297 results on '"Munnia A"'
Search Results
252. Aromatic DNA adducts and breast cancer risk: a case-cohort study within the EPIC-Spain.
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Agudo, Antonio, Peluso, Marco, Munnia, Armelle, Luján-Barroso, Leila, Barricarte, Aurelio, Amiano, Pilar, Navarro, Carmen, Sánchez, María-José, Quirós, J. Ramón, Ardanaz, Eva, Larrañaga, Nerea, Tormo, María-José, Chirlaque, María-Dolores, Rodríguez-Barranco, Miguel, Sánchez-Cantalejo, Emilio, Cellai, Filippo, Bonet, Catalina, Sala, Núria, and González, Carlos A.
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DNA adducts , *BREAST cancer risk factors , *POLYCYCLIC aromatic hydrocarbons , *EPIDEMIOLOGY , *PUBLIC health , *AROMATIC compounds , *BREAST cancer treatment - Abstract
Epidemiologic evidence linking environmental exposure to polycyclic aromatic hydrocarbons (PAH) with breast cancer is limited. Measurement of DNA adducts formed by aromatic compounds, including PAH, has been carried in breast tissue samples and white blood cells from women with breast cancer and different kinds of controls. However, these studies provide inconsistent results and bias cannot be ruled out. During the 7-year follow-up period, 305 women were diagnosed with first primary breast cancer in the EPICSpain cohort and were compared with a sample of 149 women without breast cancer at recruitment, using a case-cohort approach. Aromatic adducts to DNA from leukocytes collected at recruitment were measured by means of the 32P-post-labelling technique. The relative risk and 95% confidence interval (CI), adjusted by relevant confounders, were estimated by a modified version of Cox proportional hazards model. There was a significant increased risk for developing breast cancer when DNA adduct concentrations were doubled, with adjusted RR of 1.61 (95% CI 1.29-2.01). The increase in breast cancer risk was observed both for pre- and postmenopausal women. There was a significant interaction with tobacco smoking and body mass index, with higher effect of DNA adducts on breast cancer risk among smokers and women with normal weight. The results from our study support the hypothesis that factors leading to higher levels of aromatic DNA adducts in white blood cells may be involved in development of breast cancer. [ABSTRACT FROM AUTHOR]
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- 2017
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253. 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine adducts of workers exposed to asbestos fibers.
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Bonassi, Stefano, Cellai, Filippo, Munnia, Armelle, Ugolini, Donatella, Cristaudo, Alfonso, Neri, Monica, Milić, Mirta, Bonotti, Alessandra, Giese, Roger W., and Peluso, Marco E.M.
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ASBESTOS fibers , *SILICATE minerals , *PULMONARY fibrosis , *MESOTHELIOMA , *OXYGEN in the body , *DEOXYGUANOSINE , *OXIDATIVE stress - Abstract
Asbestos is the commercial name for a group of silicate minerals naturally occurring in the environment and widely used in the industry. Asbestos exposure has been associated with pulmonary fibrosis, mesothelioma, and malignancies, which may appear after a period of latency of 20–40 years. Mechanisms involved in the carcinogenic effects of asbestos are still not fully elucidated, although the oxidative stress theory suggests that phagocytic cells produce large amounts of reactive oxygen species, due to their inability to digest asbestos fiber. We have conducted a mechanistic study to evaluate the association between 3-(2-deoxy-β- d - erythro -pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M 1 dG) adducts, a biomarker of oxidative stress and lipid peroxidation, and asbestos exposure in the peripheral blood of 327 subjects living in Tuscany and Liguria, Italy, stratified by occupational exposure to asbestos. Adduct frequency was significantly greater into exposed subjects with respect to the controls. M 1 dG per 10 8 normal nucleotides were 4.0 ± 0.5 (SE) in 156 asbestos workers, employed in mechanic, naval, petrochemical, building industries, and in pottery and ceramic plants, versus a value of 2.3 ± 0.1 (SE) in 171 controls (p < 0.001). After stratification for occupational history, the effects persisted in 54 current asbestos workers, mainly employed in building renovation industry (2.9 ± 0.3 (SE)), and in 102 former asbestos workers (4.5 ± 0.7 (SE)), with p-values of 0.033, and <0.001, respectively. A significant effect of smoking on heavy smokers was found (p = 0.005). Our study gives additional support to the oxidative stress theory, where M 1 dG may reflect an additional potential mechanism of asbestos-induced toxicity. [ABSTRACT FROM AUTHOR]
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- 2017
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254. Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.
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Antonio Agudo, Marco Peluso, Núria Sala, Gabriel Capellá, Armelle Munnia, Sara Piro, Fátima Marín, Raquel Ibáñez, Pilar Amiano, M.José Tormo, Eva Ardanaz, Aurelio Barricarte, M.Dolores Chirlaque, Miren Dorronsoro, Nerea Larrañaga, Carmen Martínez, Carmen Navarro, J.Ramón Quirós, M.José Sánchez, and Carlos A. González
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GENETIC polymorphisms ,PHYSIOLOGICAL effects of polycyclic aromatic hydrocarbons ,DNA adducts ,BIOTRANSFORMATION (Metabolism) ,METABOLITES ,COHORT analysis - Abstract
Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the 32P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation–hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1−154C>A of CYP1A2 and the combination Tyrosine–Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10−9 normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 × 10−9adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn. [ABSTRACT FROM AUTHOR]
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- 2009
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255. DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis.
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Fabrizio Veglia, Steffen Loft, Giuseppe Matullo, Marco Peluso, Armelle Munnia, Frederica Perera, David H. Phillips, Deliang Tang, Herman Autrup, Ole Raaschou-Nielsen, Anne Tjønneland, Paolo Vineis, and for the GenairâEPIC investigators
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DNA ,AROMATIC compounds ,BIOCHEMICAL genetics ,LUNG cancer - Abstract
Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51â137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including caseâcontrol studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1â28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years. [ABSTRACT FROM AUTHOR]
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- 2008
256. 32P-Post-labelling method improvements for aromatic compound-related molecular epidemiology studies.
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Armelle Munnia, Federica Saletta, Alessandra Allione, Sara Piro, Massimo Confortini, Giuseppe Matullo, and Marco Peluso
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EPIDEMIOLOGY , *AROMATIC compounds , *DNA , *CARCINOGENS - Abstract
The 32P-post-labelling assay has emerged as a major tool for detecting bulky DNA adducts in subjects exposed to carcinogens, especially aromatic compounds. However, the 32P-post-labelling protocol still requires the use of high amounts of radioactivity, i.e. 25–50 μCi per sample, an obstacle that limits its use in large studies. The characterization of the DNA adducts measured is also limited. Methodological improvements and increased DNA adduct characterization are necessary to make this assay capable of achieving higher throughput. A new protocol was tested to ensure efficient hydrolysis to reduce the use of radioactive material and to obtain higher chromatography resolution. Different chromatography systems based on high-urea or ammonium hydroxide systems were also employed to characterize the adducts being measured. Improvements were tested by re-analysing DNA adducts in a group of police officers and urban residents in Genoa, Italy. The analysis of carcinogen-modified DNA standards was also included in the study for qualitative and quantitative comparison. An efficient DNA digestion was obtained using a method involving hydrolysis by micrococcal nuclease and a mixture of two spleen phosphodiesterases at fixed concentrations. A 72% reduction of the amount of radioactivity used for labelling was achieved in respect to the non-modified protocol without loss of DNA adduct sensitivity. An improved chromatography resolution was obtained by reducing the volume of sample to be spotted on the chromatogram. Lower volume of spotting sample can decrease sample diffusion and the formation of unresolved spots on the thin-layer chromatography plate. The amount of output produced using a single batch of carrier-free [γ-32P]ATP was increased by about 3.5-fold. A complex pattern of DNA adducts was observed in leukocytes using both high-urea or isopropanol–ammonium hydroxide systems, two techniques effective in the detection of aromatic DNA adducts. The above observations indicate that DNA adducts being measured are likely to have been induced by aromatic compounds. [ABSTRACT FROM AUTHOR]
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- 2007
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257. DNA methylation differences in exposed workers and nearby residents of the Ma Ta Phut industrial estate, Rayong, Thailand.
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Peluso, Marco, Bollati, Valentina, Munnia, Armelle, Srivatanakul, Petcharin, Jedpiyawongse, Adisorn, Sangrajrang, Suleeporn, Piro, Sara, Ceppi, Marcello, Bertazzi, Pier Alberto, Boffetta, Paolo, and Baccarelli, Andrea A
- Abstract
Background: Adverse biological effects from airborne pollutants are a primary environmental concern in highly industrialized areas. Recent studies linked air pollution exposures with altered blood Deoxyribo-nucleic acid (DNA) methylation, but effects from industrial sources and underlying biological mechanisms are still largely unexplored.Methods: The Ma Ta Phut industrial estate (MIE) in Rayong, Thailand hosts one of the largest steel, oil refinery and petrochemical complexes in south-eastern Asia. We measured a panel of blood DNA methylation markers previously associated with air pollution exposures, including repeated elements [long interspersed nuclear element-1 (LINE-1) and Alu] and genes [p53, hypermethylated-in-cancer-1 (HIC1), p16 and interleukin-6 (IL-6)], in 67 MIE workers, 65 Ma Ta Phut residents and 45 rural controls. To evaluate the role of DNA damage and oxidation, we correlated DNA methylation measures with bulky DNA and 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M(1)dG) adducts.Results: In covariate-adjusted models, MIE workers, compared with rural residents, showed lower LINE-1 (74.8% vs 78.0%; P < 0.001), p53 (8.0% vs 15.7%; P < 0.001) and IL-6 methylation (39.2% vs 45.0%; P = 0.027) and higher HIC1 methylation (22.2% vs 15.3%, P < 0.001). For all four markers, Ma Ta Phut residents exhibited methylation levels intermediate between MIE workers and rural controls (LINE-1, 75.7%, P < 0.001; p53, 9.0%, P < 0.001; IL-6, 39.8%, P = 0.041; HIC1, 17.8%, P = 0.05; all P-values vs rural controls). Bulky DNA adducts showed negative correlation with p53 methylation (P = 0.01). M(1)dG showed negative correlations with LINE-1 (P = 0.003) and IL-6 methylation (P = 0.05).Conclusions: Our findings indicate that industrial exposures may induce alterations of DNA methylation patterns detectable in blood leucocyte DNA. Correlation of DNA adducts with DNA hypomethylation suggests potential mediation by DNA damage. [ABSTRACT FROM AUTHOR]- Published
- 2012
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258. Genotoxic effects of neutrophils and hypochlorous acid.
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Güngör, Nejla, Knaapen, Ad M., Munnia, Armelle, Peluso, Marco, Haenen, Guido R., Chiu, Roland K., Godschalk, Roger W. L., and van Schooten, Frederik J.
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NEUTROPHILS , *HYPOCHLORITES , *DNA damage , *NUCLEIC acids , *GRANULOCYTES - Abstract
Chronic inflammation has been recognized as a contributing factor in the pathogenesis of lung cancer. In this process, reactive oxygen species released by neutrophils may play an important role. The aim of the present study was to investigate the capacity of the major neutrophilic oxidant hypochlorous acid (HOCl), which is formed by myeloperoxidase (MPO), to induce DNA damage and mutagenicity in lung cells. HOCl was mutagenic in lung epithelial A549 cells in vitro, showing at physiological concentrations a significant induction of mutations in the HPRT gene. We studied three major types of DNA lesions that could be relevant for this HOCl-induced mutagenicity. Single strand DNA breakage and 8-oxo-7,8-dihydro-2′-deoxyguanosine were not found to be increased following HOCl treatment. On the other hand, HOCl caused a significant increase in the formation of 3-(2-deoxy-β-D-erythro-pentofuranosyl)pyrimido[1,2-α]purin-10(3H)-one (M1dG), which can be formed by either malondialdehyde (MDA) or base propenals. We observed an increased MDA formation upon exposure of A549 cells to HOCl, but a role of base propenals cannot be excluded. In line with this, we observed 4-fold increased M1dG adduct levels in mice that were intratracheally instilled with lipopolysaccharide to induce a pulmonary inflammation with neutrophil influx. Depletion of circulating neutrophils significantly reduced pulmonary MPO activity as well as M1dG adducts levels, thereby providing a causal link between neutrophils/HOCl and pulmonary genotoxicity in vivo. Taken together, these data indicate that MPO catalysed formation of HOCl during lung inflammation should be considered as a significant source of neutrophil-induced genotoxicity. [ABSTRACT FROM PUBLISHER]
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- 2010
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259. Malondialdehyde -- deoxyguanosine adducts among workers of a Thai industrial estate and nearby residents.
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Peluso M, Srivatanakul P, Munnia A, Jedpiyawongse A, Ceppi M, Sangrajrang S, Piro S, and Boffetta P
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Background: Humans living near industrial point emissions can experience high levels of exposures to air pollutants. Map Ta Phut Industrial Estate in Thailand is the location of the largest steel, oil refinery, and petrochemical factory complexes in Southeast Asia. Air pollution is an important source of oxidative stress and reactive oxygen species, which interact with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. Objective: We measured the levels of malondialdehyde-deoxyguanosine (dG) adducts, a biomarker of oxidative stress and lipid peroxidation, in petrochemical workers, nearby residents, and subjects living in a control district without proximity to industrial sources. Design: We conducted a cross-sectional study to compare the prevalence of malondialdehyde-dG adducts in groups of subjects experiencing various degrees of air pollution. Results: The multivariate regression analysis shows that the adduct levels were associated with occupational and environmental exposures to air pollution. The highest adduct level was observed in the steel factory workers. In addition, the formation of DNA damage tended to be associated with tobacco smoking, but without reaching statistical significance. A nonsignificant increase in DNA adducts was observed after 4-6 years of employment among the petrochemical complexes. Conclusions: Air pollution emitted from the Map Ta Phut Industrial Estate complexes was associated with increased adduct levels in petrochemical workers and nearby residents. Considering the mutagenic potential of DNA lesions in the carcinogenic process, we recommend measures aimed at reducing the levels of air pollution. [ABSTRACT FROM AUTHOR]
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- 2010
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260. DNA adducts and PM10 exposure in traffic-exposed workers and urban residents from the EPIC-Florence City study
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Palli, Domenico, Saieva, Calogero, Munnia, Armelle, Peluso, Marco, Grechi, Daniele, Zanna, Ines, Caini, Saverio, Decarli, Adriano, Sera, Francesco, and Masala, Giovanna
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AIR pollution , *PARTICULATE matter , *DNA adducts , *TRAFFIC police , *TRAFFIC congestion , *DOSE-response relationship in biochemistry , *GENETIC toxicology , *CANCER risk factors - Abstract
Air pollution and particulate matter in urban areas have been associated with increased mortality from cardiovascular and respiratory diseases and increased cancer risk. Carcinogenic effects of particulate matter have been related to the contents of specific compounds, such as polycyclic aromatic hydrocarbons. The latter may form bulky DNA adducts, that may be considered as candidate markers of cancer risk. We have recently shown that traffic-exposed workers and the general population in Florence have divergent levels of DNA adducts, possibly related to different levels of exposure to genotoxic agents from vehicle emissions. In the current study, in a series of 214 Florence City healthy adults enrolled in a prospective study in the period 1993–1998 (152 residents / 62 traffic-exposed workers), we investigated the correlation between individual levels of DNA bulky adducts and PM10 exposure scores based on daily environmental measures provided by the local Environmental Protection Agency for the whole study period, by two types of urban monitoring stations (high- and low-traffic). We found that PM10 cumulative scores from high-traffic stations over the last 1–2 weeks prior to blood drawing significantly correlated (r =0.58, p =0.02) with DNA adduct levels among non-smoking traffic-exposed workers (but not among residents with no occupational exposure to vehicle emissions). A multivariate regression analysis adjusted for possible confounders confirmed these findings. PM10 scores from low-traffic stations did not show any correlation. These results show that DNA adduct levels in non-smoking workers reflect the average levels of exposure to PM10 in high-traffic urban areas experienced over a time period of 1–2 weeks. Since DNA adduct levels have been found predictive of lung cancer risk, our findings provide clues relevant to the reduction of genotoxic damage and possibly cancer risk among traffic-exposed urban workers. [Copyright &y& Elsevier]
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- 2008
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261. PHF3-specific antibody responses in over 60% of patients with glioblastoma multiforme.
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Struss, A-K, Romeike, B F M, Munnia, A, Nastainczyk, W, Steudel, W-I, König, J, Ohgaki, H, Feiden, W, Fischer, U, and Meese, E
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GLIOBLASTOMA multiforme , *MOLECULAR pathology , *TRANSCRIPTION factors - Abstract
Glioblastoma multiforme (GBM), a malignant astrocytic tumour, represents the most frequent tumour of the human brain. Nevertheless, its molecular pathology is not well understood. We utilized the immune system, which contributes to cancer protection, to help identify new GBM-related genes. By screening a human GBM cDNA library with autologous patient serum (SEREX-approach), we isolated a gene termed PHF3 (PHD finger protein 3). The gene product of PHF3 is immunogenic in GBM as tested in an allogenic patient serum screening demonstrating antibodies in 24 of 39 (61.53%) sera, whereas none of the 14 healthy persons had antibodies against PHF3. While previous SEREX studies revealed allogenic antibody responses up to 40%, our results for PHF3 represent the highest reported rate for a specific antibody response. We show that GBM patients with an antibody response against PHF3 show significant better survival than patients without PHF3-specific antibodies. Because the amino acid sequence of PHF3 contains a PHD finger (also termed LAP motif), a TFIIS homology, a proline rich region and nuclear localization signals, it supposedly functions as a transcription factor. A polyclonal antibody generated against PHF3 shows nuclear expression in most investigated formalin-fixed, paraffin embedded tissues. In GBM, PHF3 expression is concentrated in cells surrounding necroses. Oncogene (2001) 20, 4107–4114. [ABSTRACT FROM AUTHOR]
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- 2001
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262. Pool testing on random and natural clusters of individuals: Optimisation of SARS-CoV-2 surveillance in the presence of low viral load samples.
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Baccini, Michela, Rocco, Emilia, Paganini, Irene, Mattei, Alessandra, Sani, Cristina, Vannucci, Giulia, Bisanzi, Simonetta, Burroni, Elena, Peluso, Marco, Munnia, Armelle, Cellai, Filippo, Pompeo, Giampaolo, Micio, Laura, Viti, Jessica, Mealli, Fabrizia, and Carozzi, Francesca Maria
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MONTE Carlo method , *SARS-CoV-2 , *VIRAL load , *RANDOM fields - Abstract
Facing the SARS-CoV-2 epidemic requires intensive testing on the population to early identify and isolate infected subjects. During the first emergency phase of the epidemic, RT-qPCR on nasopharyngeal (NP) swabs, which is the most reliable technique to detect ongoing infections, exhibited limitations due to availability of reagents and budget constraints. This stressed the need to develop screening procedures that require fewer resources and are suitable to be extended to larger portions of the population. RT-qPCR on pooled samples from individual NP swabs seems to be a promising technique to improve surveillance. We performed preliminary experimental analyses aimed to investigate the performance of pool testing on samples with low viral load and we evaluated through Monte Carlo (MC) simulations alternative screening protocols based on sample pooling, tailored to contexts characterized by different infection prevalence. We focused on the role of pool size and the opportunity to develop strategies that take advantage of natural clustering structures in the population, e.g. families, school classes, hospital rooms. Despite the use of a limited number of specimens, our results suggest that, while high viral load samples seem to be detectable even in a pool with 29 negative samples, positive specimens with low viral load may be masked by the negative samples, unless smaller pools are used. The results of MC simulations confirm that pool testing is useful in contexts where the infection prevalence is low. The gain of pool testing in saving resources can be very high, and can be optimized by selecting appropriate group sizes. Exploiting natural groups makes the definition of larger pools convenient and potentially overcomes the issue of low viral load samples by increasing the probability of identifying more than one positive in the same pool. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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263. Wood dust and urinary 15-F2t isoprostane in Italian industry workers.
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Bono, Roberto, Capacci, Fabio, Cellai, Filippo, Sgarrella, Carla, Bellisario, Valeria, Trucco, Giulia, Tofani, Lorenzo, Peluso, Alessio, Poli, Carla, Arena, Luciano, Piro, Sara, Miligi, Lucia, Munnia, Armelle, and Peluso, Marco
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THRESHOLD limit values (Industrial toxicology) , *DUST , *WOODWORK , *DUST control , *PARANASAL sinuses , *NASAL cavity - Abstract
Wood dust is one of the most common occupational exposures, with about 3.6 million of workers in the wood industry in Europe. Wood particles can deposit in the nose and the respiratory tract and cause adverse health effects. Occupational exposure to wood dust has been associated with malignant tumors of the nasal cavity and paranasal sinuses. The induction of oxidative stress and the generation of reactive oxygen species through activation of inflammatory cells could have a role in the carcinogenicity of respirable wood dust. Therefore, we conducted a cross-sectional study to evaluate the prevalence of urinary 15-F 2t isoprostane (15-F 2t -IsoP), a biomarker of oxidative stress and peroxidation of lipids, in 123 wood workers compared to 57 unexposed controls living in Tuscany region, Italy. 15-F 2t -IsoP generation was measured by ELISA. The main result of the present study showed that a statistically significant excess of this biomarker occurred in the workers exposed to 1.48 mg/m3 of airborne wood dust with respect to the unexposed controls. The overall mean ratio (MR) between the workers exposed to wood dust and the controls was 1.36, 95% Confidence Interval (C.I.) 1.18–1.57, after correction for age and smoking habits. A significant increment of 15-F 2t -IsoP (43%) was observed in the smokers as compared to the non-smokers. The urinary excretion of 15-F 2t -IsoP was significantly associated with co-exposure to organic solvents, i.e., MR of 1.41, 95% C.I. 1.17–1.70, after adjustment for age and smoking habits. A 41% excess was observed in long-term wood workers, 95% C.I. 1.14–1.75. Multivariate regression analysis showed that the level of 15-F 2t -IsoP was linearly correlated to the length of exposure, regression coefficient (β) = 0.244 ± 0.002 (SE). The overall increment by exposure group persisted after stratification for smoking habits. For instance, in smokers, a 53% excess was detected in the wood workers as compared to the controls, 95% C.I. 1.23–1.91. Our data support the hypothesis that oxidative stress and lipid peroxidation can have a role in the toxicity of wood dust F 2 -IsoP measure can be a tool for the evaluation of the effectiveness of targeted interventions aimed to reduce exposures to environmental carcinogens. • Occupational wood dust exposure has been associated to sinonasal cancers. • Wood workers were exposed to an average value of 1.48 mg/m3 of airborne wood dust. • Significantly high concentration of urinary F 2 -IsoP was found in wood workers. • Even higher level of F 2 -IsoP was detected with concomitant carcinogen exposure. • F 2 -IsoP amount was associated to occupational history. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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264. Paternal Exposure to Environmental Chemical Stress Affects Male Offspring's Hepatic Mitochondria.
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Godschalk, Roger, Remels, Alex, Hoogendoorn, Camiel, Benthem, Jan van, Luijten, Mirjam, Duale, Nur, Brunborg, Gunnar, Olsen, Ann-Karin, Bouwman, Freek G, and Munnia, Armelle
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PHYSIOLOGICAL effects of benzopyrene , *MITOCHONDRIA , *OXIDATIVE stress , *DNA damage , *GENE expression , *PHENOTYPES , *MESSENGER RNA - Abstract
Preconceptional paternal exposures may affect offspring's health, which cannot be explained by mutations in germ cells, but by persistent changes in the regulation of gene expression. Therefore, we investigated whether pre-conceptional paternal exposure to benzo[a]pyrene (B[a]P) could alter the offspring's phenotype. Male C57BL/6 mice were exposed to B[a]P by gavage for 6 weeks, 3x per week, and were crossed with unexposed BALB-c females 6 weeks after the final exposure. The offspring was kept under normal feeding conditions and was sacrificed at 3 weeks of age. Analysis of the liver proteome by 2D-gel electrophoresis and mass spectrometry indicated that proteins involved in mitochondrial function were significantly downregulated in the offspring of exposed fathers. This down-regulation of mitochondrial proteins was paralleled by a reduction in mitochondrial DNA copy number and reduced activity of citrate synthase and b-hydroxyacyl-CoA dehydrogenase, but in male offspring only. Surprisingly, analysis of hepatic mRNA expression revealed a male-specific up-regulation of the genes, whose proteins were downregulated, including Aldh2 and Ogg1. This discrepancy could be related to several selected microRNA (miRNA)'s that regulate the translation of these proteins; miRNA-122, miRNA-129-2-5p, and miRNA-1941 were upregulated in a gender-specific manner. Since mitochondria are thought to be a source of intracellular reactive oxygen species, we additionally assessed oxidatively-induced DNA damage. Both 8-hydroxy-deoxyguanosine and malondialdehyde-dG adduct levels were significantly reduced in male offspring of exposed fathers. In conclusion, we show that paternal exposure to B[a]P can regulate mitochondrial metabolism in offspring, which may have profound implications for our understanding of health and disease risk inherited from fathers. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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265. Intrauterine exposure to flavonoids modifies antioxidant status at adulthood and decreases oxidative stress-induced DNA damage
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Vanhees, Kimberly, van Schooten, Frederik J., van Waalwijk van Doorn-Khosrovani, Sahar Barjesteh, van Helden, Stefan, Munnia, Armelle, Peluso, Marco, Briedé, Jacob J., Haenen, Guido R.M.M., and Godschalk, Roger W.L.
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FLAVONOIDS , *ANTIOXIDANTS , *OXIDATIVE stress , *DNA damage , *CHRONIC diseases , *DISEASE susceptibility - Abstract
Abstract: Maternal intake of flavonoids, known for their antioxidant properties, may affect the offspring''s susceptibility to developing chronic diseases at adult age, especially those related to oxidative stress, via developmental programming. Therefore, we supplemented female mice with the flavonoids genistein and quercetin during gestation, to study their effect on the antioxidant capacity of lung and liver of adult offspring. Maternal intake of quercetin increased the expression of Nrf2 and Sod2 in fetal liver at gestational day 14.5. At adult age, in utero exposure to both flavonoids resulted in the increased expression of several enzymatic antioxidant genes, which was more pronounced in the liver than in the adult lung. Moreover, prenatal genistein exposure induced the nonenzymatic antioxidant capacity in the adult lung, partly by increasing glutathione levels. Prenatal exposure to both flavonoids resulted in significantly lower levels of oxidative stress-induced DNA damage in liver only. Our observations lead to the hypothesis that a preemptive trigger of the antioxidant defense system in utero had a persistent effect on antioxidant capacity and as a result decreased oxidative stress-induced DNA damage in the liver. [Copyright &y& Elsevier]
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- 2013
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266. Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents.
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Peluso, Marco, Srivatanakul, Petcharin, Jedpiyawongse, Adisorn, Sangrajrang, Suleeporn, Munnia, Armelle, Piro, Sara, Ceppi, Marcello, Boffetta, Paolo, Godschalk, Roger W. L., and van Schooten, Frederik J.
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LUNG cancer risk factors , *DNA adducts , *INDUSTRIAL districts , *INDUSTRIAL toxicology , *AIR pollution , *POLYCYCLIC aromatic hydrocarbons - Abstract
The Map-Ta-Phut Industrial Estate (MIE) in Rayong, Thailand, is the location of one of the largest industrial complexes in southeastern Asia. The MIE complex produces a mixture of air pollutants, including polycyclic aromatic hydrocarbons, compounds capable to induce the generation of DNA adducts. DNA adducts are considered to be a biomarker of carcinogen exposure; however, its production can be modulated by genetic susceptibility. Thus, we analysed the influence of EPHX1 His139Arg (A>G, rs2234922) and NQO1 Pro187Ser (C>T, rs1800566) involved in the metabolism of polycyclic aromatic hydrocarbons; MnSOD2 Val16Ala (C>T, rs1799725) a gene that acts against the free radical generation; APE1/Ref-1 Asp148Glu (T>G, rs3136820) a gene involved in the repair of DNA, and in the control of cell-cycle and apoptosis on leucocyte DNA adducts in 77 MIE workers, 69 Map-Ta-Phut residents, and 50 rural controls, Rayong, Thailand. We searched for associations with the ‘sum of at-risk alleles’ by combining the variant alleles of EPHX1, NQO1 and MnSOD2 together with the wild-type allele of APE1, since they appeared to influence lung cancer risk. Although our findings revealed significant associations between DNA adducts and the EPHX1 His139Arg and NQO1 Pro187Ser polymorphisms, the combination of at-risk alleles was found to affect DNA damage much stronger. DNA adducts were significantly increased in the individuals bearing 4 and ≥5 at-risk alleles [mean ratio (MR) = 1.55, 95% CI 1.10–2.18, P = 0.012, and MR = 2.11, 95% CI 1.27–3.51, P = 0.004, respectively)]. After correction for residence/employment categorisation, a significant increment was present in the MIE workers with ≥5 alleles (MR = 2.88, 95% CI 1.46–5.71, P = 0.003). Our data indicate relationships between the generation of DNA adducts and the enzymatic activities of EPHX and NQO1. The combination of unfavourable genetic variants seems to determine the individuals’ susceptibility, rather than a single polymorphism. [ABSTRACT FROM PUBLISHER]
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- 2013
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267. Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung.
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Van Helden, Yvonne G. J., Keijer, Jaap, Heil, Sandra G., Picó, Catalina, Palou, Andreu, Oliver, Paula, Munnia, Armelle, Briedé, Jacob J., Peluso, Marco, Franssen-van Hal, Nicole L., Van Schooten, Frederik J., and Godschalk, Roger W. L.
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BETA carotene , *LUNG cancer , *CIGARETTE smokers , *RADICALS (Chemistry) , *EPITHELIAL cells - Abstract
Beta-carotene (BC) was found to enhance lung cancer risk in smokers. This adverse effect was unexpected because BC was thought to act as an anti-oxidant against cigarette smoke-derived radicals. These radicals can directly or indirectly damage DNA, leading to the formation of pro-mutagenic DNA lesions such as 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dG) and 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG). Later, it was suggested that high concentrations of BC could also result in pro-oxidant effects. Therefore, we investigated whether high but physiologically feasible concentrations of BC were able to alter (i) the formation of radicals in vitro assessed by electron spin resonance spectroscopy, (ii) the levels of 8-oxo-dG and M1dG in vitro in lung epithelial cells after incubation with hydrogen peroxide (H2O2) and the smoke-derived carcinogen benzo[a]pyrene (B[a]P) and (iii) the levels of 8-oxo-dG and M1dG in vivo in ferrets’ lung after chronic exposure to B[a]P. BC increased in vitro hydroxyl radical formation in the Fenton reaction but inhibited the formation of carbon-centered radicals. Similarly, BC was able to enhance 8-oxo-dG in vitro in lung epithelial cells. On the other hand, BC significantly inhibited M1dG formation in lung epithelial cells, especially after induction of M1dG by H2O2 or B[a]P. Finally, BC supplementation of ferrets also resulted in a significant decrease in M1dG, but in contrast to the in vitro experiments, no effect was observed on 8-oxo-dG levels, probably because of increased base excision repair capacities as assessed by a modified comet assay. These data indicate that the fate of BC being a pro- or anti-oxidant strongly depends on the type of radical involved. [ABSTRACT FROM PUBLISHER]
- Published
- 2009
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268. « L’influence du modèle prosodique hugolien sur la poésie ouvrière de la Monarchie de Juillet »
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Gleizes, Delphine, Institut d’Histoire des Représentations et des Idées dans les Modernités (IHRIM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hélène Millot, Nathalie Vincent-Munnia, Marie-Claude Schapira, Michèle Fontana, École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Gleizes, Delphine
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[SHS.LITT] Humanities and Social Sciences/Literature ,Poésie populaire ,littérature XIXe siècle ,[SHS.LITT]Humanities and Social Sciences/Literature ,Littérature -- 19e siècle ,ComputingMilieux_MISCELLANEOUS ,Victor Hugo - Abstract
International audience
- Published
- 2005
269. Hyperglycemia and microRNAs in prostate cancer.
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Russo V, Tamburrino L, Morselli S, Sani C, Baldi E, Sebastianelli A, Raspollini MR, Mongia A, Carradori V, Lallo E, Munnia A, Bisanzi S, Marchiani S, Visioli C, Rapi S, Serni S, Zappa M, Carozzi F, and Peluso M
- Abstract
Background: Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa., Methods: Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient., Results: When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships., Conclusions: miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2024
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270. Traffic-Related Air Pollution and Ground-Level Ozone Associated Global DNA Hypomethylation and Bulky DNA Adduct Formation.
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Munnia A, Bollati V, Russo V, Ferrari L, Ceppi M, Bruzzone M, Dugheri S, Arcangeli G, Merlo F, and Peluso M
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- Humans, DNA Adducts genetics, DNA Damage, Biomarkers, Ozone toxicity, Air Pollutants toxicity, Air Pollutants analysis, Air Pollution adverse effects, Air Pollution analysis
- Abstract
Studies have indicated that air pollution, including surface-level ozone (O
3 ), can significantly influence the risk of chronic diseases. To better understand the carcinogenic mechanisms of air pollutants and identify predictive disease biomarkers, we examined the association between traffic-related pollutants with DNA methylation alterations and bulky DNA adducts, two biomarkers of carcinogen exposure and cancer risk, in the peripheral blood of 140 volunteers-95 traffic police officers, and 45 unexposed subjects. The DNA methylation and adduct measurements were performed by bisulfite-PCR and pyrosequencing and32 P-postlabeling assay. Airborne levels of benzo(a)pyrene [B(a)P], carbon monoxide, and tropospheric O3 were determined by personal exposure biomonitoring or by fixed monitoring stations. Overall, air pollution exposure was associated with a significant reduction (1.41 units) in global DNA methylation (95% C.I. -2.65-0.04, p = 0.026). The decrement in ALU repetitive elements was greatest in the policemen working downtown (95% C.I. -3.23--0.49, p = 0.008). The DNA adducts were found to be significantly increased (0.45 units) in the municipal officers with respect to unexposed subjects (95% C.I. 0.02-0.88, p = 0.039), mainly in those who were controlling traffic in downtown areas (95% C.I. 0.39-1.29, p < 0.001). Regression models indicated an increment of ALU methylation at higher B(a)P concentrations (95% C.I. 0.03-0.60, p = 0.032). Moreover, statistical models showed a decrement in ALU methylation and an increment of DNA damage only above the cut-off value of 30 µg/m3 O3 . A significant increment of 0.73 units of IL-6 gene methylation was also found in smokers with respect to non-smokers. Our results highlighted the role of air pollution on epigenetic alterations and genotoxic effects, especially above the target value of 30 µg/m3 surface-level O3 , supporting the necessity for developing public health strategies aimed to reduce traffic-related air pollution molecular alterations.- Published
- 2023
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271. Cruciferous Vegetable Intake and Bulky DNA Damage within Non-Smokers and Former Smokers in the Gen-Air Study (EPIC Cohort).
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Peluso M, Munnia A, Russo V, Galli A, Pala V, Schouw YTV, Schulze MB, Weiderpass E, Tumino R, Saieva C, Exezarreta Pilar A, Aune D, Heath AK, Aglago E, Agudo A, Panico S, Petersen KEN, Tjønneland A, Cirera L, Rodriguez-Barranco M, Katzke V, Kaaks R, Ricceri F, Milani L, Vineis P, and Sacerdote C
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- DNA Damage, Diet, Dietary Fiber, Humans, Non-Smokers, Prospective Studies, Smokers, Smoking adverse effects, Vegetables, Brassicaceae, Neoplasms
- Abstract
Epidemiologic studies have indicated that cruciferous vegetables can influence the cancer risk; therefore, we examined with a cross-sectional approach the correlation between the frequent consumption of the total cruciferous vegetables and the formation of bulky DNA damage, a biomarker of carcinogen exposure and cancer risk, in the Gen-Air study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. DNA damage measurements were performed in the peripheral blood of 696 of those apparently healthy without cancer controls, including 379 never-smokers and 317 former smokers from seven European countries by the 32P-postlabeling assay. In the Gen-Air controls, the median intake of cruciferous vegetables was 6.16 (IQR 1.16−13.66) g/day, ranging from 0.37 (IQR 0−6.00) g/day in Spain to 11.34 (IQR 6.02−16.07) g/day in the UK. Based on this information, participants were grouped into: (a) high consumers (>20 g/day), (b) medium consumers (3−20 g/day) and (c) low consumers (<3.0 g/day). Overall, low cruciferous vegetable intake was correlated with a greater frequency of bulky DNA lesions, including benzo(a)pyrene, lactone and quinone-adducts and bulky oxidative lesions, in the adjusted models. Conversely, a high versus low intake of cruciferous vegetables was associated with a reduction in DNA damage (up to a 23% change, p = 0.032); this was particularly evident in former smokers (up to a 40% change, p = 0.008). The Generalized Linear Regression models indicated an overall Mean Ratio between the high and the low consumers of 0.78 (95% confidence interval, 0.64−0.97). The current study suggests that a higher intake of cruciferous vegetables is associated with a lower level of bulky DNA adducts and supports the potential for cancer prevention strategies through dietary habit changes aimed at increasing the consumption of cruciferous vegetables.
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- 2022
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272. DNA damage and genomic instability among workers formerly and currently exposed to asbestos.
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Milić M, Neri M, Ceppi M, Bruzzone M, Munnia A, Ugolini D, Cristaudo A, Bonotti A, Peluso ME, and Bonassi S
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- Cross-Sectional Studies, European Union, Humans, Male, Micronucleus Tests methods, Middle Aged, Occupational Health, Risk Assessment, Surveys and Questionnaires, Asbestos adverse effects, DNA Damage genetics, Genomic Instability genetics, Occupational Exposure standards
- Abstract
Objectives Despite an asbestos ban in the European Union, exposure to asbestos still represents an occupational risk. Biomarkers of DNA damage and genomic instability in groups exposed to asbestos may contribute to the identification of subgroups/subjects at higher risk. Methods A cross-sectional study was conducted on 468 male individuals (80 working in occupational settings with potential exposure to asbestos fibers, 202 retired workers with past exposure, and 186 non-exposed controls) to compare genomic instability, cell proliferation and differentiation level using the non-invasive micronucleus buccal cytome assay. Data on demographic variables, lifestyle, and occupational history were collected with a standardized questionnaire. Micronuclei (MN) and other biomarkers of DNA damage and genomic instability were scored in a minimum of 2000/1000 cells per individual, respectively. Results Univariate and multivariate analysis showed opposite associations of MN frequency with current and former exposure. Compared to unexposed controls, workers with current potential exposure to asbestos had 55% lower MN frequency [95% confidence interval (CI) 71-29%, P<0.001] while those with past exposure had 34% higher MN frequency (95% CI 1-77%, P<0.001). The frequency of cells with condensed chromatin and binucleated cells was elevated among formerly exposed workers. The multivariate analysis did not reveal any actual confounders, although lower MN frequency was observed among subjects eating fresh fruit or vegetables every day or taking vitamin supplements. Conclusions Active workers with potential exposure to asbestos fibers did not show increased genomic damage. On the contrary, workers exposed in the past experienced a persistently elevated genomic instability, which may be used for risk assessment at subgroup or individual level.
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- 2018
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273. Linking the generation of DNA adducts to lung cancer.
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Ceppi M, Munnia A, Cellai F, Bruzzone M, and Peluso MEM
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- Case-Control Studies, Humans, Lung Neoplasms diagnosis, Lung Neoplasms epidemiology, Prognosis, Protective Factors, Risk Assessment, Risk Factors, Smoking epidemiology, Smoking genetics, Smoking Cessation, Smoking Prevention, Biomarkers, Tumor genetics, DNA Adducts genetics, Lung chemistry, Lung Neoplasms genetics, Smoking adverse effects
- Abstract
Worldwide, lung cancer is the leading cause of cancer death. DNA adducts are considered a reliable biomarker that reflects carcinogen exposure to tobacco smoke, but the central question is what is the relationship of DNA adducts and cancer? Therefore, we investigated this relationship by a meta-analysis of twenty-two studies with bronchial adducts for a total of 1091 subjects, 887 lung cancer cases and 204 apparently healthy individuals with no evidence of lung cancer. Our study shows that these adducts are significantly associated to increase lung cancer risk. The value of Mean Ratio
lung-cancer (MR) of bronchial adducts resulting from the random effects model was 2.64, 95% C.I. 2.00-3.50, in overall lung cancer cases as compared to controls. The significant difference, with lung cancer patients having significant higher levels of bronchial adducts than controls, persisted after stratification for smoking habits. The MRlung-cancer value between lung cancer patients and controls for smokers was 2.03, 95% C.I. 1.42-2.91, for ex-smokers 3.27, 95% C.I. 1.49-7.18, and for non-smokers was 3.81, 95% C.I. 1.85-7.85. Next, we found that the generation of bronchial adducts is significantly related to inhalation exposure to tobacco smoke carcinogens confirming its association with volatile carcinogens. The MRsmoking estimate of bronchial adducts resulting from meta-regression was 2.28, 95% Confidence Interval (C.I.) 1.10-4.73, in overall smokers in respect to non-smokers. The present work provides strengthening of the hypothesis that bronchial adducts are not simply relate to exposure, but are a cause of chemical-induced lung cancer., (Copyright © 2017 Elsevier B.V. All rights reserved.)- Published
- 2017
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274. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.
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Cellai F, Munnia A, Viti J, Doumett S, Ravagli C, Ceni E, Mello T, Polvani S, Giese RW, Baldi G, Galli A, and Peluso MEM
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- Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, DNA Adducts analysis, DNA Adducts genetics, Hep G2 Cells, Humans, Lipid Peroxidation, Liver Neoplasms genetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, Carcinoma, Hepatocellular therapy, DNA Damage, Hyperthermia, Induced methods, Liver Neoplasms therapy, Magnetite Nanoparticles therapeutic use, Oxidative Stress
- Abstract
Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using
32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.- Published
- 2017
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275. Bulky DNA Adducts, Tobacco Smoking, Genetic Susceptibility, and Lung Cancer Risk.
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Munnia A, Giese RW, Polvani S, Galli A, Cellai F, and Peluso MEM
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- Humans, Lung Neoplasms epidemiology, Tobacco Smoking epidemiology, DNA Adducts genetics, Genetic Predisposition to Disease, Lung Neoplasms genetics, Tobacco Smoking genetics
- Abstract
The generation of bulky DNA adducts consists of conjugates formed between large reactive electrophiles and DNA-binding sites. The term "bulky DNA adducts" comes from early experiments that employed a
32 P-DNA postlabeling approach. This technique has long been used to elucidate the association between adducts and carcinogen exposure in tobacco smoke studies and assess the predictive value of adducts in cancer risk. Molecular data showed increased DNA adducts in respiratory tracts of smokers vs nonsmokers. Experimental studies and meta-analysis demonstrated that the relationship between adducts and carcinogens was linear at low doses, but reached steady state at high exposure, possibly due to metabolic and DNA repair pathway saturation and increased apoptosis. Polymorphisms of metabolic and DNA repair genes can increase the effects of environmental factors and confer greater likelihood of adduct formation. Nevertheless, the central question remains as to whether bulky adducts cause human cancer. If so, lowering them would reduce cancer incidence. Pooled and meta-analysis has shown that smokers with increased adducts have increased risk of lung cancer. Adduct excess in smokers, especially in prospective longitudinal studies, supports their use as biomarkers predictive of lung cancer., (© 2017 Elsevier Inc. All rights reserved.)- Published
- 2017
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276. Oxidatively damaged DNA in the nasal epithelium of workers occupationally exposed to silica dust in Tuscany region, Italy.
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Peluso ME, Munnia A, Giese RW, Chellini E, Ceppi M, and Capacci F
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- Adult, Cross-Sectional Studies, DNA Adducts drug effects, Female, Follow-Up Studies, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Nasal Mucosa drug effects, Occupational Diseases chemically induced, Occupational Diseases pathology, Oxidation-Reduction, Prognosis, DNA Damage drug effects, Dust, Nasal Mucosa pathology, Occupational Diseases epidemiology, Occupational Exposure adverse effects, Oxidative Stress drug effects, Silicon Dioxide adverse effects
- Abstract
Unlabelled: Chronic silica exposure has been associated to cancer and silicosis. Furthermore, the induction of oxidative stress and the generation of reactive oxygen species have been indicated to play a main role in the carcinogenicity of respirable silica. Therefore, we conducted a cross-sectional study to evaluate the prevalence of 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M1dG) adducts, a biomarker of oxidative stress and peroxidation of lipids, in the nasal epithelium of 135 silica-exposed workers, employed in pottery, ceramic and marble manufacturing plants as well as in a stone quarry, in respect to 118 controls living in Tuscany region, Italy. The M1dG generation was measured by the (32)P-postlabelling assay. Significant higher levels of M1dG adducts per 10(8) normal nucleotides were observed in the nasal epithelium of smokers, 77.9±9.8 (SE), and in those of former smokers, 80.7±9.7 (SE), as compared to non-smokers, 57.1±6.2 (SE), P = 0.001 and P = 0.004, respectively. Significant increments of M1dG adducts were found in the nasal epithelium of workers that handle artificial marble conglomerates, 184±36.4 (SE), and in those of quarry workers, 120±34.7 (SE), with respect to controls, 50.6±2.7 (SE), P = 0.014 and P < 0.001, respectively. Null increments were observed in association with the pottery and the ceramic factories. After stratification for different exposures, silica-exposed workers that were co-exposed to organic solvents, and welding and exhaust fumes have significantly higher M1dG levels, 90.4±13.4 (SE), P = 0.014 vs., Control: Our data suggested that silica exposure might be associated with genotoxicity in the nasal epithelial cells of silica-exposed workers that handle of artificial marble conglomerates and quarry workers. Importantly, we observed that co-exposures to other respiratory carcinogens may have contributed to enhance the burden of M1dG adducts in the nasal epithelium of silica-exposed workers., (© The Author 2015. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
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277. Bisphenol-A exposures and behavioural aberrations: median and linear spline and meta-regression analyses of 12 toxicity studies in rodents.
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Peluso ME, Munnia A, and Ceppi M
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- Aggression drug effects, Animals, Anxiety chemically induced, Anxiety psychology, Dose-Response Relationship, Drug, Female, Gestational Age, Linear Models, Male, Maternal Exposure adverse effects, Memory drug effects, Mice, Pregnancy, Prenatal Exposure Delayed Effects, Rats, Risk Assessment, Sex Factors, Spatial Learning drug effects, Time Factors, Behavior, Animal drug effects, Benzhydryl Compounds toxicity, Endocrine Disruptors toxicity, Phenols toxicity
- Abstract
Exposures to bisphenol-A, a weak estrogenic chemical, largely used for the production of plastic containers, can affect the rodent behaviour. Thus, we examined the relationships between bisphenol-A and the anxiety-like behaviour, spatial skills, and aggressiveness, in 12 toxicity studies of rodent offspring from females orally exposed to bisphenol-A, while pregnant and/or lactating, by median and linear splines analyses. Subsequently, the meta-regression analysis was applied to quantify the behavioural changes. U-shaped, inverted U-shaped and J-shaped dose-response curves were found to describe the relationships between bisphenol-A with the behavioural outcomes. The occurrence of anxiogenic-like effects and spatial skill changes displayed U-shaped and inverted U-shaped curves, respectively, providing examples of effects that are observed at low-doses. Conversely, a J-dose-response relationship was observed for aggressiveness. When the proportion of rodents expressing certain traits or the time that they employed to manifest an attitude was analysed, the meta-regression indicated that a borderline significant increment of anxiogenic-like effects was present at low-doses regardless of sexes (β)=-0.8%, 95% C.I. -1.7/0.1, P=0.076, at ≤120 μg bisphenol-A. Whereas, only bisphenol-A-males exhibited a significant inhibition of spatial skills (β)=0.7%, 95% C.I. 0.2/1.2, P=0.004, at ≤100 μg/day. A significant increment of aggressiveness was observed in both the sexes (β)=67.9,C.I. 3.4, 172.5, P=0.038, at >4.0 μg. Then, bisphenol-A treatments significantly abrogated spatial learning and ability in males (P<0.001 vs. females). Overall, our study showed that developmental exposures to low-doses of bisphenol-A, e.g. ≤120 μg/day, were associated to behavioural aberrations in offspring., (Copyright © 2014. Published by Elsevier Ireland Ltd.)
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- 2014
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278. Aberrant methylation of hypermethylated-in-cancer-1 and exocyclic DNA adducts in tobacco smokers.
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Peluso ME, Munnia A, Bollati V, Srivatanakul P, Jedpiyawongse A, Sangrajrang S, Ceppi M, Giese RW, Boffetta P, and Baccarelli AA
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- Adult, CpG Islands drug effects, Dose-Response Relationship, Drug, Epigenesis, Genetic drug effects, Female, Humans, Linear Models, Male, Middle Aged, Multivariate Analysis, Risk Factors, Smoking metabolism, Smoking Cessation, Smoking Prevention, Thailand, DNA Adducts analysis, DNA Methylation drug effects, Kruppel-Like Transcription Factors genetics, Malondialdehyde analysis, Smoke adverse effects, Smoking adverse effects, Smoking genetics
- Abstract
Tobacco smoke has been shown to produce both DNA damage and epigenetic alterations. However, the potential role of DNA damage in generating epigenetic changes is largely underinvestigated in human studies. We examined the effects of smoking on the levels of DNA methylation in genes for tumor protein p53, cyclin-dependent kinase inhibitor2A, hypermethylated-in-cancer-1 (HIC1), interleukin-6, Long Interspersed Nuclear Element type1, and Alu retrotransposons in blood of 177 residents in Thailand using bisulfite-PCR andpyrosequencing. Then, we analyzed the relationship of this methylation with the oxidative DNA adduct, M₁dG (a malondialdehyde adduct), measured by ³²P-postlabeling. Multivariate statistical analyses showed that HIC1 methylation levels were significantly increased in smokers compared with nonsmokers (p ≤ .05). A dose response was observed, with the highest HIC1 methylation levels in smokers of ≥ 10 cigarettes/day relative to nonsmokers and intermediate values in smokers of 1-9 cigarettes/day (p for trend ≤ .001). No additional relationships were observed. We also evaluated correlations between M₁dG and the methylation changes at each HIC1 CpG site individually. The levels of this adduct in smokers showed a significant linear correlation with methylation at one of the 3 CpGs evaluated in HIC1: hypermethylation at position 1904864340 was significantly correlated with the adduct M₁dG (covariate-adjusted regression coefficient (β) = .224 ± .101 [SE], p ≤ .05). No other correlations were detected. Our study extends prior work by others associating hypermethylation of HIC1 with smoking; shows that a very specific hypermethylation event can arise from smoking; and encourages future studies that explore a possible role for M₁dG in connecting smoking to this latter hypermethylation.
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- 2014
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279. DNA adducts and combinations of multiple lung cancer at-risk alleles in environmentally exposed and smoking subjects.
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Peluso ME, Munnia A, Srivatanakul P, Jedpiyawongse A, Sangrajrang S, Ceppi M, Godschalk RW, van Schooten FJ, and Boffetta P
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- DNA-(Apurinic or Apyrimidinic Site) Lyase genetics, Environmental Exposure, Epoxide Hydrolases genetics, Genetic Predisposition to Disease, Genetic Variation, Humans, NAD(P)H Dehydrogenase (Quinone) genetics, Risk, Superoxide Dismutase genetics, DNA Adducts, DNA Damage, Lung Neoplasms genetics, Smoking, Tobacco Smoke Pollution
- Abstract
Interindividual variation in DNA adduct levels in individuals exposed to similar amounts of environmental carcinogens may be due to genetic variability. We analysed the influence of genes involved in determining/modifying DNA damage, including microsomal epoxide hydrolase1 (EPHX1) His139Arg, N-acetyl-transferase, NAD(P)H:quinone oxidoreductase1 (NQO1) Pro187Ser, manganese superoxide dismutase2 (MnSOD2) Val16Ala, and apurinic/apyrimidinic endonuclease1 (APE1) Asp148Glu polymorphisms in blood of 120 smokers. Subsequently, we examined the effects of the combinations of the variant alleles of EPHX, NQO1 and MnSOD2 together with the wild type allele of APE1 on DNA damage by calculating the "sum of at-risk alleles." We reviewed the studies examining the relationships of DNA adducts with at-risk alleles in environmentally exposed subjects. Our findings showed that smokers carrying the EPHX1-139Arg and the NQO1-187Ser variants were significantly more likely to have higher adduct levels. Null associations were found with the other variants. Nevertheless, DNA adduct levels in smokers with ≥5 at-risk alleles were significantly different from those with fewer than two alleles. A similar picture emerged from studies of DNA adducts and at-risk alleles in environmentally exposed and smoking subjects. Certain at-risk allele combinations may confer a greater likelihood of increased levels of adducts after environmental insults. The increase in DNA adduct levels in susceptible subjects exposed to environmental carcinogens may reflect changes in the mechanisms that protect cells from the accumulation of genetic damage. Alterations of the physiological processes designed to maintain homeostasis may reduce the individual "genotoxic tolerance" to environmental challenges and result in phenotypes characterized by high levels of DNA adducts., (© 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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280. Malondialdehyde-deoxyguanosine and bulky DNA adducts in schoolchildren resident in the proximity of the Sarroch industrial estate on Sardinia Island, Italy.
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Peluso M, Munnia A, Ceppi M, Giese RW, Catelan D, Rusconi F, Godschalk RW, and Biggeri A
- Subjects
- Adolescent, Air Pollution, Child, Female, Humans, Islands, Italy, Male, Nasal Mucosa metabolism, Rural Population, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Urban Population, Volatile Organic Compounds adverse effects, DNA Adducts chemistry, Deoxyguanosine chemistry, Malondialdehyde chemistry, Occupational Exposure adverse effects
- Abstract
Air quality is a primary environmental concern in highly industrialised areas, with potential health effects in children residing nearby. The Sarroch industrial estate in Cagliari province, Sardinia Island, Italy, hosts the world's largest power plant and the second largest European oil refinery and petrochemical park. This industrial estate produces a complex mixture of air pollutants, including benzene, heavy metals and polycyclic aromatic hydrocarbons. Thus, we conducted a cross-sectional study to evaluate the prevalence of malondialdehyde-deoxyguanosine adducts in the nasal epithelium of 75 representative children, aged 6-14 years, attending primary and secondary schools in Sarroch in comparison with 73 rural controls. Additionally, the levels of bulky DNA adducts were analysed in a subset of 62 study children. DNA damage was measured by (32)P-postlabelling methodologies. The air concentrations of benzene and ethyl benzene were measured in the school gardens of Sarroch and a rural village by diffusive samplers. Outdoor measurements were also performed in other Sarroch areas and in the proximity of the industrial estate. The outdoor levels of benzene and ethyl benzene were significantly higher in the school gardens of Sarroch than in the rural village. Higher concentrations were also found in other Sarroch areas and in the vicinity of the industrial park. The mean levels of malondialdehyde-deoxyguanosine adducts per 10(8) normal nucleotides ± standard error (SE) were 74.6±9.1 and 34.1±4.4 in the children from Sarroch and the rural village, respectively. The mean ratio was 2.53, 95% confidence interval (CI): 1.71-2.89, P < 0.001, versus rural controls. Similarly, the levels of bulky DNA adducts per 10(8) normal nucleotides ± SE were 2.9±0.4 and 1.6±0.2 in the schoolchildren from Sarroch and the rural village, respectively. The means ratio was 1.90, 95% CI: 1.25-2.89, P = 0.003 versus rural controls. Our study indicates that children residing near the industrial estate have a significant increment of DNA damage.
- Published
- 2013
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281. Exocycilic DNA Adducts in a Murine Model of Non-alcoholic Steatohepatitis.
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Peluso MEM, Munnia A, Tarocchi M, Arciello M, Balsano C, Giese RW, and Galli A
- Abstract
Introduction: Non-alcoholic fatty liver disease is the most common hepatic disorder in Western countries. The transition from abnormal accumulation of lipids toward non-alcoholic steatohepatitis (NASH) represents a key step in the development of chronic liver pathologies. Oxidative stress and lipid peroxidation have often been proposed as mechanisms in the progression to steatohepatitis., Methods: We have examined the hepatic levels of exocyclic DNA adducts, indicated from 3-(2-deoxy-β-D-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3H)-one deoxyguanosine (M
1 dG) adduct, a biomarker of oxidative stress and lipid peroxidation, in a murine model of NASH using the32 P-DNA postlabeling assay., Results: Our findings show that C57BL/6 mice fed with high-fat and cholesterol diet developed signs associated with NASH after eight weeks, whereas there was no evidence of steatosis in control mice. The score for steatohepatitis ranged from grade 2 to 3 for steatosis, inflammation, and fibrosis, showing that the experimental diet was able to induce pathologic alterations of the parenchyma in eight weeks. Higher levels of M1 dG adducts were detected in the livers of C57BL/6 mice which developed experimental NASH after eight weeks of high-fat and cholesterol feed, 5.6 M1 dG ± 0.4 (SE) per 106 total nucleotides, as compared to control mice, 1.6 M1 dG ± 0.4 (SE). The statistical analysis showed that the increment of oxidatively damaged DNA in mice with NASH raised on high-fat and cholesterol diet was statistically significant as compared to control mice, P=0.006., Conclusions: Our report suggests a link between NASH and M1 dG in experimental animals fed with a diet rich in saturated fats and cholesterol. High-fat and cholesterol may act together in inducing a broader spectrum of oxidatively damaged DNA, including exocyclic DNA adducts, that may contribute to the decline of hepatocyte functions, from disturbance of critical pathways, such as transcription and replication, triggering transient or permanent cell-cycle arrest and cell-death, up to chromosomal instability.- Published
- 2013
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282. Bulky DNA adducts and breast cancer risk in the prospective EPIC-Italy study.
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Saieva C, Peluso M, Masala G, Munnia A, Ceroti M, Piro S, Sera F, Bendinelli B, Pala V, Sieri S, Tumino R, Giurdanella MC, Panico S, Mattiello A, Vineis P, Polidoro S, Matullo G, and Palli D
- Subjects
- Breast Neoplasms epidemiology, Case-Control Studies, Female, Genetic Predisposition to Disease, Humans, Incidence, Italy epidemiology, Leukocytes chemistry, Middle Aged, Molecular Epidemiology, Odds Ratio, Prospective Studies, Registries, Regression Analysis, Risk Assessment, Risk Factors, Time Factors, Breast Neoplasms genetics, Carcinogens, Environmental adverse effects, DNA Adducts analysis, Leukocytes drug effects
- Abstract
The role of environmental carcinogen exposure in breast cancer development has long been suspected, but no specific association has been identified so far. A few molecular epidemiology studies reported that DNA adducts detected by different methods are associated with a modest increase of breast cancer risk. We aimed to evaluate the association between bulky DNA adducts, detected by the (32)P-postlabelling method in peripheral leukocytes, and the risk of developing breast cancer in the female Italian cohorts of the EPIC (European Prospective Investigation into Cancer and nutrition) study. By using a nested case-control design, breast cancer cases identified in the follow-up of over 30,000 women of EPIC-Italy study have been matched to controls by specific criteria. We measured the levels of bulky DNA adducts by the (32)P-postlabelling method in peripheral leukocytes donated at enrolment. Conditional regression analyses adjusted for selected potential confounders were used. Results on DNA adduct levels were available for 292 cases and 292 matched controls. The mean DNA adduct levels were similar in both groups (P=0.62). Multivariate regression analyses failed to show any significant association between bulky DNA adducts and breast cancer. Our results do not support any association of breast cancer risk with exposure to environmental carcinogens as measured through the levels of bulky DNA adducts in pre-diagnostic white blood cells. Larger studies by using different methods and/or biomarkers are needed to better evaluate the role of specific environmental carcinogens in breast carcinogenesis.
- Published
- 2011
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283. Prevention of silica health effects in Italy: current challenges for the Occupational Health and Safety Unit of the Italian National Health Service.
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Giovanazzi A, Chellini E, Fubini B, Capacci F, Ferris F, Di Rico R, Peluso M, Tomatis M, Munnia A, Carnevale F, Loi AM, Arcari C, and Sciarra G
- Subjects
- Carcinogens, Humans, Italy, Lung Neoplasms epidemiology, Occupational Diseases epidemiology, Occupational Health, Lung Neoplasms chemically induced, Occupational Diseases chemically induced, Occupational Exposure adverse effects, Occupational Exposure prevention & control, Silicon Dioxide adverse effects
- Abstract
Background: Since its foundation in 2002, the Italian Silica Network (NIS), a collaborative network of professionals and public authorities, has been engaged in several aspects of research, control, and prevention of silica exposure and effects, and also in support for compensation claims for silica-related occupational health effects in Italy., Methods: We start with a report on the NIS point of view concerning the recent scientific results (from epidemiology and laboratory studies), including those carried out by NIS in cooperation with Italian universities and other public agencies. This is followed by a description of the data on silica exposure in different Italian workplaces and guidelines for the management of occupational exposure to silica, as developed by two model regional programmes for the ceramics industry, metal foundries and tunnel excavation., Results: The NIS initiatives highlighted the persistence of workplace conditions posing a significant risk for silica-related health effects, particularly in small industries and workshops. Experimental work has also shown that a number of physical and chemical factors affect the bioreactivity of silica particles., Conclusion: Based on NIS experience, it appears clear that currently conditions exist in Italy so as to positively contribute to the WHO Programme for the eradication of silicosis and the other diseases related to silica exposure. In order to achieve this goal, a coordinated and wide-ranging effort is required to reduce the wide gap in specific prevention activities, particularly in small industries and workshops, where high levels of silica exposure sometimes occur.
- Published
- 2011
284. Bulky DNA adducts in white blood cells: a pooled analysis of 3,600 subjects.
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Ricceri F, Godschalk RW, Peluso M, Phillips DH, Agudo A, Georgiadis P, Loft S, Tjonneland A, Raaschou-Nielsen O, Palli D, Perera F, Vermeulen R, Taioli E, Sram RJ, Munnia A, Rosa F, Allione A, Matullo G, and Vineis P
- Subjects
- Female, Humans, Male, Seasons, DNA Adducts analysis, DNA Adducts blood, Leukocytes
- Abstract
Background: Bulky DNA adducts are markers of exposure to genotoxic aromatic compounds, which reflect the ability of an individual to metabolically activate carcinogens and to repair DNA damage. Polycyclic aromatic hydrocarbons (PAHs) represent a major class of carcinogens that are capable of forming such adducts. Factors that have been reported to be related to DNA adduct levels include smoking, diet, body mass index (BMI), genetic polymorphisms, the season of collection of biologic material, and air pollutants., Methods: We pooled 11 studies (3,600 subjects) in which bulky DNA adducts were measured in human white blood cells with similar (32)P-postlabeling techniques and for which a similar set of variables was available, including individual data on age, gender, ethnicity, batch, smoking habits, BMI, and season of blood collection, and a limited set of gene variants., Results: Lowest DNA adduct levels (P = 0.006) were observed in the spring (median = 0.50 adducts per 10(8) nucleotides), followed by summer (0.64), autumn (0.70), and winter (0.85). The same pattern emerged in multivariate analysis but only among never smokers (P = 0.02). Adduct levels were significantly lower (P = 0.001) in northern Europe (the Netherlands and Denmark; mean = 0.60, median = 0.40) than in southern Europe (Italy, Spain, France, and Greece; mean = 0.79, median = 0.60)., Conclusions: In this large pooled analysis, we have found only weak associations between bulky DNA adducts and exposure variables. Seasonality (with higher adducts levels in winter) and air pollution may partly explain some of the interarea differences (north vs. south Europe), but most inter-area and interindividual variations in adduct levels still remain unexplained., Impact: Our study describes the largest pooled analysis of bulky DNA adducts so far, showing that interindividual variation is still largely unexplained, though seasonality seems to play a role., (©2010 AACR.)
- Published
- 2010
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285. Malondialdehyde-deoxyguanosine adduct formation in workers of pathology wards: the role of air formaldehyde exposure.
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Bono R, Romanazzi V, Munnia A, Piro S, Allione A, Ricceri F, Guarrera S, Pignata C, Matullo G, Wang P, Giese RW, and Peluso M
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- Adult, Air Pollutants, Occupational analysis, Biomarkers blood, Biomarkers metabolism, DNA Adducts blood, Deoxyguanosine blood, Dose-Response Relationship, Drug, Female, Formaldehyde analysis, Humans, Italy epidemiology, Leukocytes pathology, Male, Malondialdehyde blood, Reproducibility of Results, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Air Pollutants, Occupational toxicity, DNA Adducts biosynthesis, Deoxyguanosine biosynthesis, Environmental Exposure analysis, Formaldehyde toxicity, Leukocytes drug effects, Malondialdehyde metabolism
- Abstract
Formaldehyde is an ubiquitous pollutant to which humans are exposed. Pathologists can experience high formaldehyde exposure levels. Formaldehyde-among other properties-induce oxidative stress and free radicals, which react with DNA and lipids, leading to oxidative damage and lipid peroxidation, respectively. We measured the levels of air-formaldehyde exposure in a group of Italian pathologists and controls. We analyzed the effect of formaldehyde exposure on leukocyte malondialdehyde-deoxyguanosine adducts (M(1)-dG), a biomarker of oxidative stress and lipid peroxidation. We studied the relationship between air-formaldehyde and M(1)-dG adducts. Air-formaldehyde levels were measured by personal air samplers. M(1)-dG adducts were analyzed by a (32)P-postlabeling assay. Reduction room pathologists were significantly exposed to air-formaldehyde with respect to controls and to the pathologists working in other laboratory areas (p < 0.001). A significant difference for M(1)-dG adducts between exposed pathologists and controls was found (p = 0.045). The effect becomes stronger when the evaluation of air-formaldehyde exposure was based on personal samplers (p = 0.018). Increased M(1)dG adduct levels were only found in individuals exposed to air-formaldehyde concentrations higher than 66 microg/m(3). When the exposed workers and controls were subgrouped according to smoking, M(1)-dG tended to increase in all of the subjects, but a significant association between M(1)-dG and air-formaldehyde was only found in nonsmokers (p = 0.009). Air-formaldehyde played a role positive but not significant (r = 0.355, p = 0.075, Pearson correlation) in the formation of M(1)-dG, only in nonsmokers. Working in the reduction rooms and exposure to air-formaldehyde concentrations higher than 66 microg/m(3) are associated with increased levels of M(1)-dG adducts.
- Published
- 2010
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286. Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort.
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Agudo A, Peluso M, Sala N, Capellá G, Munnia A, Piro S, Marín F, Ibáñez R, Amiano P, Tormo MJ, Ardanaz E, Barricarte A, Chirlaque MD, Dorronsoro M, Larrañaga N, Martínez C, Navarro C, Quirós JR, Sánchez MJ, and González CA
- Subjects
- Acetylation, Adult, Aged, Aryl Hydrocarbon Hydroxylases genetics, Aryl Hydrocarbon Hydroxylases metabolism, Arylamine N-Acetyltransferase genetics, Arylamine N-Acetyltransferase metabolism, Arylsulfotransferase genetics, Arylsulfotransferase metabolism, Cohort Studies, DNA Adducts genetics, Epoxide Hydrolases genetics, Epoxide Hydrolases metabolism, Female, Glutathione Transferase genetics, Glutathione Transferase metabolism, Humans, Hydrolysis, Male, Middle Aged, Oxidation-Reduction, DNA Adducts blood, Leukocytes enzymology, Polycyclic Aromatic Hydrocarbons metabolism, Polymorphism, Genetic
- Abstract
Aromatic compounds such as polycyclic aromatic hydrocarbons, arylamines and heterocyclic amines require metabolic activation to form metabolites able to bind to DNA, a process mediated by polymorphic enzymes. We measured aromatic DNA adducts in white blood cells by the (32)P-post-labelling assay in a sample of 296 healthy adults (147 men and 149 women) from five regions of Spain. We also analyzed functional polymorphisms in the metabolic genes CYP1A1, CYP1A2, EPHX1, GSTM1, GSTT1, NAT2 and SULT1A1. A significant increased level of DNA aromatic adducts was found related to the fast oxidation-hydrolysis phenotype defined by the polymorphism I462V in CYP1A1, the allele A in IVS1-154C>A of CYP1A2 and the combination Tyrosine-Arginine for Y113H and H139R of EPHX1. Geometric means (adducts per 10(-9) normal nucleotides) were 2.17, 4.04 and 6.30 for slow, normal and fast phenotypes, respectively (P-trend = 0.01). Slow acetylation by NAT2 was associated with a significant decrease in adduct level; subjects with slow alleles *5A and *7A/B had in average 1.56 x 10(-9)adducts, as compared with 5.60 for those with normal NAT2 activity (P-value = 0.01). No association was seen with polymorphisms of other metabolic genes such as GSTM1, GSTT1 or SULT1A1. We concluded that the metabolic pathways of oxidation, hydrolysis and acetylation are relevant to the formation of bulky DNA adducts. This could suggest a potential involvement of aromatic compounds in the formation of such adducts; however, given lack of specificity of the post-labeling assay, a firm conclusion cannot be drawn.
- Published
- 2009
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287. 32P-Post-labelling method improvements for aromatic compound-related molecular epidemiology studies.
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Munnia A, Saletta F, Allione A, Piro S, Confortini M, Matullo G, and Peluso M
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- Animals, Chromatography, High Pressure Liquid methods, Chromatography, Thin Layer methods, DNA Adducts drug effects, Humans, Indicators and Reagents analysis, Mice, Carcinogens pharmacology, DNA analysis, DNA Damage drug effects, Leukocytes drug effects, Liver drug effects, Molecular Epidemiology, Phosphorus Radioisotopes
- Abstract
The (32)P-post-labelling assay has emerged as a major tool for detecting bulky DNA adducts in subjects exposed to carcinogens, especially aromatic compounds. However, the (32)P-post-labelling protocol still requires the use of high amounts of radioactivity, i.e. 25-50 muCi per sample, an obstacle that limits its use in large studies. The characterization of the DNA adducts measured is also limited. Methodological improvements and increased DNA adduct characterization are necessary to make this assay capable of achieving higher throughput. A new protocol was tested to ensure efficient hydrolysis to reduce the use of radioactive material and to obtain higher chromatography resolution. Different chromatography systems based on high-urea or ammonium hydroxide systems were also employed to characterize the adducts being measured. Improvements were tested by re-analysing DNA adducts in a group of police officers and urban residents in Genoa, Italy. The analysis of carcinogen-modified DNA standards was also included in the study for qualitative and quantitative comparison. An efficient DNA digestion was obtained using a method involving hydrolysis by micrococcal nuclease and a mixture of two spleen phosphodiesterases at fixed concentrations. A 72% reduction of the amount of radioactivity used for labelling was achieved in respect to the non-modified protocol without loss of DNA adduct sensitivity. An improved chromatography resolution was obtained by reducing the volume of sample to be spotted on the chromatogram. Lower volume of spotting sample can decrease sample diffusion and the formation of unresolved spots on the thin-layer chromatography plate. The amount of output produced using a single batch of carrier-free [gamma-(32)P]ATP was increased by about 3.5-fold. A complex pattern of DNA adducts was observed in leukocytes using both high-urea or isopropanol-ammonium hydroxide systems, two techniques effective in the detection of aromatic DNA adducts. The above observations indicate that DNA adducts being measured are likely to have been induced by aromatic compounds.
- Published
- 2007
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288. Bronchial malondialdehyde DNA adducts, tobacco smoking, and lung cancer.
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Munnia A, Bonassi S, Verna A, Quaglia R, Pelucco D, Ceppi M, Neri M, Buratti M, Taioli E, Garte S, and Peluso M
- Subjects
- Aged, Bronchi metabolism, Cyclin D1 genetics, DNA Damage, DNA Repair, Female, Genotype, Humans, Lung Neoplasms metabolism, Male, Malondialdehyde analysis, Middle Aged, Polymorphism, Genetic, Risk Factors, Bronchi drug effects, DNA Adducts, Lung Neoplasms etiology, Malondialdehyde metabolism, Smoking adverse effects
- Abstract
Tobacco smoking is a major risk factor for lung cancer causing, among other effects, oxidative stress and lipid peroxidation. Malondialdehyde (MDA)-DNA adducts can be induced by direct DNA oxidation and by lipid peroxidation. We measured the relationship between bronchial MDA-DNA adducts and tobacco smoking, cancer status, and selected polymorphisms in 43 subjects undergoing a bronchoscopic examination for diagnostic purposes. MDA-DNA adducts were higher in current smokers than in never smokers (frequency ratio (FR) = 1.51, 95% confidence interval (CI) 1.01-2.26). MDA-DNA adducts were also increased in lung cancer cases with respect to controls, but only in smokers (FR = 1.70, 95% CI 1.16-2.51). Subjects with GA and AA cyclin D1 (CCND1) genotypes showed higher levels of MDA-DNA adducts than those with the wild-type genotype (FR = 1.51 (1.04-2.20) and 1.45 (1.02-2.07)). Lung cancer cases with levels of MDA-DNA adducts over the median showed a worse, but not statistically significant, survival, after adjusting for age, gender, and packyears (hazard ratio = 2.48, 95% CI 0.65-9.44). Our findings reinforce the role of smoking in lung carcinogenesis through oxidative stress. Subjects who carry at least one variant allele of the CCND1 gene could accumulate DNA damage for altered cell-cycle control and reduced DNA repair proficiency.
- Published
- 2006
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289. Randomized controlled trial: effects of diet on DNA damage in heavy smokers.
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Talaska G, Al-Zoughool M, Malaveille C, Fiorini L, Schumann B, Vietas J, Peluso M, Munnia A, Bianchini M, Allegro G, Matullo G, Sacerdote C, and Vineis P
- Subjects
- DNA Adducts urine, Dietary Supplements, Flavonoids, Humans, Male, Smoking genetics, Urinary Bladder cytology, Vegetables, DNA Damage, Diet, Smoking adverse effects
- Abstract
We have conducted a randomized trial which investigated the ability of dietary changes (in particular diets rich in cruciferous vegetables and flavonoids), to increase urinary antimutagenicity and inhibit DNA damage in smokers. Ninety heavy smokers were recruited and randomly assigned to three groups, and were given three different diets. The first diet was based on flavonoid-rich foods, particularly cruciferous vegetables, but not based on supplementation; the second was a normal isocaloric diet (with an adequate administration of fruits and vegetables); and the third was based on supplementation of flavonoids in the form of green tea and soy products. DNA adducts were measured by (32)P-postlabelling in exfoliated bladder cells at different times since the start of the trial. In spite of randomization, subjects in the control group smoked more than those in the experimental groups, and this can explain the higher adduct levels at baseline. A slight decrease in bulky DNA adducts in exfoliated bladder cells was observed after 1 year since the end in the supplementation group and after 1 month in white blood cells. The only statistically significant association was found in a regression model that adjusted for smoking, in which the increase in flavonoid intake was associated with a decrease in adducts after 1 year (P = 0.02). These data suggest that adherence to a diet rich in cruciferous vegetables and flavonoids might reduce genotoxicity in the human urinary bladder of smokers, but they should be interpreted with caution owing to small numbers and the uneven distribution of smoking habits in the experimental groups. Smoking is the most important single preventable cause of cancer; at the present stage of knowledge it is totally unlikely that certain dietary habits can seriously counteract the effects of tobacco smoking.
- Published
- 2006
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290. Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival.
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Pallasch CP, Struss AK, Munnia A, König J, Steudel WI, Fischer U, and Meese E
- Subjects
- Autoantibodies, Brain Neoplasms radiotherapy, DNA-Binding Proteins, Female, Glioblastoma mortality, Glioblastoma radiotherapy, Humans, Male, Middle Aged, Survival Analysis, Time Factors, Treatment Outcome, Antigens, Neoplasm immunology, Biomarkers, Tumor immunology, Brain Neoplasms immunology, Brain Neoplasms surgery, Glioblastoma immunology, Glioblastoma surgery, Transcription Factors immunology
- Abstract
Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma-expressed antigens including GLEA1, GLEA2 and PHD-finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1-autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma-associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma., ((c) 2005 Wiley-Liss, Inc.)
- Published
- 2005
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291. Exocyclic malondialdehyde and aromatic DNA adducts in larynx tissues.
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Munnia A, Amasio ME, and Peluso M
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- Aged, Alcohol Drinking, Carcinogens, DNA chemistry, DNA Damage, Environment, Female, Free Radicals, Humans, Laryngeal Neoplasms metabolism, Larynx pathology, Lipid Peroxidation, Male, Middle Aged, Smoking, DNA Adducts, Larynx drug effects, Malondialdehyde pharmacology
- Abstract
Cigarette smoking and alcohol consumption, known to cause free radical generation and lipid peroxidation, are established risk factors for larynx cancer. Malondialdehyde (MDA) is a naturally occurring product of lipid peroxidation, capable of interacting with DNA to form exocyclic MDA-DNA adducts. In the present study, we investigated if the production of MDA-DNA adducts was increased in larynx cancer patients with respect to controls using (32)P-DNA postlabeling techniques. Moreover, we examined the potential effects of cigarette smoking and alcohol consumption on endogenous DNA adducts. We then analyzed the same set of larynx tissues for the presence of (32)P-postlabeled aromatic DNA adducts to determine more about the levels and types of adducts formed in the larynx. We observed that cancer patients tended to have increased levels of MDA and aromatic DNA adducts with respect to controls. In addition, smoking and alcohol were found to influence the formation of endogenous adducts in the larynx tissues. Finally, the amounts of endogenous adducts were found to be comparable to those observed for aromatic DNA adducts in the same set of larynx tissues. These findings imply that endogenous lesions, if not repaired, may contribute to larynx cancer development.
- Published
- 2004
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292. Combination of DNA repair gene single nucleotide polymorphisms and increased levels of DNA adducts in a population-based study.
- Author
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Matullo G, Peluso M, Polidoro S, Guarrera S, Munnia A, Krogh V, Masala G, Berrino F, Panico S, Tumino R, Vineis P, and Palli D
- Subjects
- Alleles, Analysis of Variance, DNA Adducts blood, Humans, Italy epidemiology, Leukocytes metabolism, Neoplasms epidemiology, Odds Ratio, Polymorphism, Restriction Fragment Length, Prospective Studies, Sequence Analysis, DNA, Xeroderma Pigmentosum genetics, DNA Adducts metabolism, DNA Repair genetics, Neoplasms genetics, Polymorphism, Single Nucleotide
- Abstract
Inherited single nucleotide polymorphisms (SNPs) of DNA repair genes may contribute to variations in DNA repair capacity and susceptibility to cancer. We investigated the role of SNPs in three DNA repair genes (X-ray repair cross-complementing group 1-Arg399Gln, exon 10; X-ray repair cross-complementing group 3-Thr241Met, exon 7; and xeroderma pigmentosum-D-Lys751Gln, exon 23) and their combination, in modulating the levels of "bulky" DNA adducts in a population sample of 628 Italian healthy individuals belonging to the prospective European project "European Prospective Investigation into Cancer and Nutrition." DNA-adduct levels were measured as relative adduct level per 10(9) nucleotides by (32)P-post DNA labeling assay in WBCs from peripheral blood. Genotyping was performed by PCR-RFLP analysis or primer extension/denaturing high-performance liquid chromatography technique. We found a dose-response relationship between the number of at-risk alleles and levels of adducts (P = 0.0046). Individuals with at least three variant alleles had a statistically significant odds ratio (OR) for being in the highest tertile of adducts compared with those with undetectable adducts [three alleles, adjusted OR = 5.07, 95% confidence interval (CI) = 1.29-19.9; four alleles, adjusted OR = 5.03, 95% CI = 1.18-21.45; five alleles, adjusted OR = 7.65, 95% CI = 0.94-62.2]. Our study suggests that the combined effect of multiple variant alleles may be more important than the investigation of single SNP in modulating DNA repair capacity.
- Published
- 2003
293. Expression, cellular distribution and protein binding of the glioma amplified sequence (GAS41), a highly conserved putative transcription factor.
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Munnia A, Schütz N, Romeike BF, Maldener E, Glass B, Maas R, Nastainczyk W, Feiden W, Fischer U, and Meese E
- Subjects
- Amino Acid Sequence, Animals, Base Sequence, DNA, Complementary chemistry, Humans, Immunohistochemistry, Molecular Sequence Data, Protein Binding, Transcription Factors chemistry, Transcription Factors genetics, Transcription Factors analysis
- Abstract
The glioma amplified sequence 41 (GAS41) was previously isolated by microdissection mediated cDNA capture from the glioblastoma multiforme cell line TX3868 and shown to be frequently amplified in human gliomas. We determined the complete cDNA sequence of the GAS41 gene, demonstrated that the GAS41 protein is evolutionarily conserved, specifically at the N-terminus, and identified the yeast transcription factor tf2f domain within the GAS41 sequence. A human multiple-tissue Northern blot revealed ubiquitous expression of GAS41 with the highest expression in human brain. After generating polyclonal antibodies we found GAS41 protein expression in the nucleus of the TX3868 cell line by Western blot analysis and immunofluorescence microscopy. The nuclear localization was confirmed for several human tumors including gliomas of different grades of malignancy. In neuroblastoma however, GAS41 was found in the nucleoli but not in the nucleoplasm. Yeast two-hybrid screening of the TX3868 cell line identified the nuclear mitotic apparatus protein (NuMA), the KIAA1009 protein, and prefoldin subunit 1 (PFDN1) as potential interacting partners of GAS41. We generated a polyclonal antibody against the KIAA1009 protein and we demonstrated that the KIAA1009 protein is a nuclear protein, which appears to be co-localized with the GAS41 protein and NuMA.
- Published
- 2001
- Full Text
- View/download PDF
294. Analysis of 13 (32)P-DNA postlabeling studies on occupational cohorts exposed to air pollution.
- Author
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Peluso M, Ceppi M, Munnia A, Puntoni R, and Parodi S
- Subjects
- Air Pollutants, Occupational analysis, Benzo(a)pyrene adverse effects, Benzo(a)pyrene analysis, Humans, Occupational Exposure, Phosphorus Radioisotopes metabolism, Polycyclic Aromatic Hydrocarbons adverse effects, Polycyclic Aromatic Hydrocarbons analysis, Statistics, Nonparametric, Air Pollutants, Occupational adverse effects, DNA Adducts blood
- Abstract
Industrial and urban workers may be exposed to significant levels of air pollutants resulting from the incomplete combustion of organic matter. The authors performed a meta-analysis of 13 DNA-adduct studies ((32)P-DNA postlabeling technique) on occupational cohorts exposed to air pollution. The association between levels of DNA adducts and air pollution exposure was significant both in heavily exposed industrial workers and in less severely exposed urban workers. Moreover, in an analysis using the seven studies that reported measuring levels of benzo[a]pyrene (B(a)P), a typical marker of exposure, DNA adduct levels in exposed workers (versus those in referents) were significantly correlated with air levels of B(a)P. The relation between DNA adducts and B(a)P was found to be linear at low doses and sublinear at high doses, indicating that DNA adduct formation tends to reach some kind of saturation point at higher levels of exposure to the chemical mixtures present in fumes. When the authors examined the efficiency of DNA adduct production associated with increasing air pollution exposures, the production of DNA adducts per unit of exposure was significantly decreased at higher B(a)P exposure levels. These findings suggest that linear downward extrapolations based on DNA adduct levels associated with B(a)P concentrations of > or =20 ng/m(3) might be affected by underestimation bias.
- Published
- 2001
- Full Text
- View/download PDF
295. Novel tankyrase-related gene detected with meningioma-specific sera.
- Author
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Monz D, Munnia A, Comtesse N, Fischer U, Steudel WI, Feiden W, Glass B, and Meese EU
- Subjects
- Amino Acid Sequence, Blotting, Northern, Cloning, Molecular, DNA Primers chemistry, Gene Library, Humans, Molecular Sequence Data, Poly(ADP-ribose) Polymerases genetics, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Meningeal Neoplasms blood, Meningioma blood, Tankyrases
- Abstract
In many meningiomas, alterations of chromosome 22 can be found, and the NF2 (neurofibromatosis type 2) gene, in particular, is of great interest as a putative gene involved in meningioma. Because the NF2 gene is not mutated in all meningiomas, additional genes may be involved. Instead of looking for alterations directly at the DNA level, we used the immune response of meningioma patients to identify immunogenic antigens that may be associated with the disease. We screened a fetal brain cDNA expression library with sera pools from different patients bearing meningioma classified according to the three WHO grades, using the serological identification of antigens by recombinant expression cloning immunological screening method. Here, we report the finding of a new tankyrase-related protein. We found 16 overlapping clones with homologies to tankyrase when we screened the library with the common-type meningioma sera pool and 2 such clones when we screened the library with the atypical meningioma sera. The anaplastic meningioma sera did not identify any tankyrase-related clones. We tested some of the newly identified clones with 13 single sera, 6 of which (37.5%) reacted positively with the tankyrase-related clones. In addition, we screened the tankyrase-related clone with six sera pools from individuals without obvious disease. Although 1 of 24 (4.2%) normal sera reacted with the tankyrase-related clone, we found a striking difference in the frequency of reactivity to this clone by sera from patients bearing tumors corresponding to the three WHO meningioma grades; common-type sera was the most frequently reactive. Northern blot analysis demonstrates expression of the novel tankyrase gene in two common-type meningiomas from patients with immune response.
- Published
- 2001
296. 32P-postlabeling detection of aromatic adducts in the white blood cell DNA of nonsmoking police officers.
- Author
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Peluso M, Merlo F, Munnia A, Valerio F, Perrotta A, Puntoni R, and Parodi S
- Subjects
- Adult, Autoradiography, DNA Adducts genetics, Female, Humans, Italy, Male, Phosphorus Radioisotopes, Police, Air Pollutants, Occupational blood, Benzo(a)pyrene adverse effects, Biomarkers blood, Carcinogens adverse effects, DNA Adducts blood, Environmental Pollutants adverse effects, Leukocytes metabolism
- Abstract
Atmosphere in urban areas may be polluted by a number of combustion sources, including industries, vehicle traffic, and residential heating. Traffic police constitute a group of workers that is highly exposed to urban pollutants, especially those from motor vehicle exhaust. We conducted a biomonitoring study to simultaneously measure in 34 nonsmoking police officers and in 36 nonsmoking office workers, as referents, the individual benzo(a)pyrene [B(a)P] exposure using personal samplers and the formation of DNA adducts in peripheral WBCs using 32P-postlabeling techniques. Our results show that the police officers were exposed to significantly higher levels of B(a)P than were referents (P < 0.0001). No seasonal variation of the atmospheric levels of B(a)P was found throughout the year. The median relative adduct labeling x 10(-8) values of the controls and exposed police officers were 0.94 (range, 0.1-3.7) and 1.3 (range, 0.1-5.5), respectively, using the nuclease P1 technique. Although the DNA adduct levels of police officers were globally higher than those of referents (P < 0.05), the difference was entirely due to the summer difference [median values 0.80 (range, 0.1-1.8) and 2.8 (range, 0.7-5.5), respectively (P < 0.001)]. In winter, the DNA adduct levels were substantially identical, and in midseason, there was only a very small increase in police officers, with respect to controls (statistically not significant). Moreover, a more significant seasonal variation of bulky aromatic DNA adduct levels was observed in WBC DNA samples of police officers (P < 0.05) compared to those of referents. The seasonal variation of bulky aromatic adduct levels could be correlated with the reported seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes.
- Published
- 1998
297. (32)P-postlabeling detection of DNA adducts in peripheral white blood cells of greenhouse floriculturists from western Liguria, Italy.
- Author
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Peluso M, Merlo F, Munnia A, Bolognesi C, Puntoni R, and Parodi S
- Subjects
- Adult, Age Factors, Aged, Agriculture, Butanols, Case-Control Studies, Chromatography, Ion Exchange, Confidence Intervals, DNA analysis, Female, Humans, Italy, Male, Middle Aged, Odds Ratio, Phosphorus Isotopes, Sex Factors, Single-Strand Specific DNA and RNA Endonucleases, DNA Adducts analysis, Leukocytes metabolism, Occupational Exposure, Pesticides adverse effects
- Abstract
Pesticides are widely used in agriculture to enhance crop yields and to control disease vectors. Floriculturists work frequently in greenhouses and may be exposed to high levels of pesticides, which may result in adverse health effects. To evaluate the relationship between exposure to pesticides and DNA adduct formation in peripheral WBCs of Italian floriculturists, the nuclease P1 modification of a (32)P-postlabeling assay was used to analyze WBC DNA from floriculturists (n = 26) and matched controls (n = 22). DNA adduct-positive samples were more frequent in floriculturists (11/26; 42%) than in matched controls (2/22; 9%) (P < 0.01). Slightly higher frequencies of DNA adduct-positive samples were observed in floriculturists > or = 44 years of age (53%) and in female floriculturists (57%). Floricultural practice was found to be associated with a significantly higher DNA adduct-positive rate in WBCs (rate ratio, 5.12; 95% confidence interval, 1.1-23.7) after allowing for the effects of age and gender. These two latter covariates were not significantly associated with DNA adduct-positive rates. The quantitative levels of DNA adducts were significantly higher in floriculturists than in matched controls according to the Mann-Whitney nonparametric statistic (P = 0.0052). The median adduct level for positive samples among floriculturists was 1.5/10(8) bases. A specific, well-visible spot, named alpha adduct, was detected in 7 out of the 11 DNA adduct-positive samples from floriculturists but in none of the (22 + 20) referent samples (P = 0.0004). The presence of pesticide-related DNA adducts was confirmed clearly using the butanol extraction procedure. Six of 8 floriculturists and 0 of 10 referents were found positive with this method. The median adduct level for positive samples was 6.0/10(8) bases. Two strong spots close to the origin could be identified in all six positive floriculturists, using the butanol extraction procedure. No association between DNA adducts and use of specific pesticides was observed.
- Published
- 1996
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