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IntroductionThe advanced maternal age (AMA) pregnancies escalate rapidly, which are frequently linked to higher risks of adverse outcomes. Advanced maternal age (AMA) placenta exhibited premature aging, presumably resulting in trophoblast dysfunction, inadequate placentation. However, the precise reasons and mechanisms of trophoblast aging in AMA placenta remain unclear, posing a significant limitation to provide effective guidance for prenatal healthcare in clinical settings. Notably, the organism shows heightened vulnerability to oxidative damage as it ages. YAP (Yes-associated protein) was reported to play a critical role in regulation of aging and resisting oxidative damage, yet these roles had not been elucidated in the placenta. Therefore, this study explored the relationship between trophoblast cell aging and oxidative injury and YAP in AMA pregnancy, which not only provided an insight into the mechanisms of trophoblast cell aging, but also provide valuable directions for healthcare during AMA pregnancy.MethodsIn this study, human term placentas were collected from AMA and normal pregnancies for the analysis of aging, oxidative damage and YAP level. HTR8/SVneo cells were manipulated with (hydrogen peroxide) H2O2 to explore the effects of oxidative damage on trophoblast cell senescence and YAP levels. YAP expression in HTR8/SVneo cells was manipulated to investigate its role in trophoblastic senescence and oxidative damage.ResultsCompared with the control group, the AMA placenta exhibits increased aging biomarkers, which is coupled with an elevation in oxidative damage within placental trophoblast cells and a notable decline in YAP levels. Cellular experiments demonstrated that oxidative damage from H2O2 triggered trophoblast cell senescence and resulted in a reduction of YAP levels. Furthermore, employing molecular modification to silence YAP expression in these cells led to an induction of aging. Conversely, overexpressing YAP ameliorated both trophoblast cell aging and the associated DNA oxidative damage that arised from H2O2.ConclusionThe decline of YAP in AMA pregnancy should be responsible for the increased oxidative injury and premature placenta aging, indicating that YAP plays a significant role in combating oxidative damage and delaying aging, thereby providing a new guidance for prenatal care in AMA pregnancies. Maintaining YAP levels or implementing anti-oxidative stress interventions could potentially mitigate the incidence of complications involved AMA pregnancy.

Fine particulate matter (PM2.5) increases the risks of lung cancer. Epigenetics provides a new toxicology mechanism for the adverse health effects of PM2.5. However, the regulating mechanisms of PM2.5 exposure on candidate gene DNA methylation changes in the development of lung cancer remain unclear. Abnormal expression of the glutathione S transferase (GST) gene is associated with cancer. However, the relationship between PM2.5 and DNA methylation-mediated GST gene expression is not well understood. In this study, we performed GST DNA methylation analysis and GST-related gene expression in human A549 cells exposed to PM2.5 (0, 50, 100 µg/mL, from Taiyuan, China) for 24 h (n = 4). We found that PM2.5 may cause DNA oxidative damage to cells and the elevation of GSTP1 promotes cell resistance to reactive oxygen species (ROS). The Kelch-1ike ECH-associated protein l (Keap1)/nuclear factor NF-E2-related factor 2 (Nrf2) pathway activates the GSTP1. The decrease in the DNA methylation level of the GSTP1 gene enhances GSTP1 expression. GST DNA methylation is associated with reduced levels of 5-methylcytosine (5mC), DNA methyltransferase 1 (DNMT1), and histone deacetylases 3 (HDAC3). The GSTM1 was not sensitive to PM2.5 stimulation. Our findings suggest that PM2.5 activates GSTP1 to defend PM2.5-induced ROS and 8-hydroxy-deoxyguanosine (8-OHdG) formation through the Keap1/Nrf2 signaling pathway and GSTP1 DNA methylation. [ABSTRACT FROM AUTHOR]

The direct photoionization of DNA canonical bases under ultraviolet radiation is difficult due to the high ionization potentials. According to previous quantum chemical calculations, methylation can have great influence on the ionization potential. Are methylated nucleobases prone to photoionization and cause DNA damage? As an important epigenetic modification in transcription, expression, and regulation of genes, it is of great biological significance to explore the effect of methylation on base photoionization from the experimental perspective. Herein, we study the photoionization behavior of methylated purines 6 mA and 6mG at 266 nm using a nanosecond transient UV–Vis spectroscopy. The hydrated electron and methylated base radicals are observed, indicating the occurrence of photoionization for both 6mG and 6 mA. We measured one‐photon ionization yields to be (5.0 ± 0.2) × 10−3 and (1.4 ± 0.2) × 10−3 for 6mG and 6 mA, respectively. These are higher than those of (dA)20 and (dA20)·(dT20) previously reported, indicating that methylation significantly promotes base photoionization with a stronger effect than base stacking, consistent with calculations in literature. Given that the hydrated electrons and methylated base radicals from photoionization can trigger a cascade of deleterious reactions, the methylated purine bases may act as hotspots of DNA photoionization damage of living organisms. [ABSTRACT FROM AUTHOR]

Exposure to coal mining dust poses a substantial health hazard to individuals due to the complex mixture of components released during the extraction process. This study aimed to assess the oxidative potential of residual coal mining dust on human lymphocyte DNA and telomeres and to perform a chemical characterization of coal dust and urine samples. The study included 150 individuals exposed to coal dust for over ten years, along with 120 control individuals. The results revealed significantly higher levels of DNA damage in the exposed group, as indicated by the standard comet assay, and oxidative damage, as determined by the FPG-modified comet assay. Moreover, the exposed individuals exhibited significantly shorter telomeres compared to the control group, and a significant correlation was found between telomere length and oxidative DNA damage. Using the PIXE method on urine samples, significantly higher concentrations of sodium (Na), phosphorus (P), sulfur (S), chlorine (Cl), potassium (K), iron (Fe), zinc (Zn), and bromine (Br) were observed in the exposed group compared to the control group. Furthermore, men showed shorter telomeres, greater DNA damage, and higher concentrations of nickel (Ni), calcium (Ca), and chromium (Cr) compared to exposed women. Additionally, the study characterized the particles released into the environment through GC–MS analysis, identifying several compounds, including polycyclic aromatic hydrocarbons (PAHs) such as fluoranthene, naphthalene, anthracene, 7H-benzo[c]fluorene, phenanthrene, pyrene, benz[a]anthracene, chrysene, and some alkyl derivatives. These findings underscore the significant health risks associated with exposure to coal mining dust, emphasizing the importance of further research and the implementation of regulatory measures to safeguard the health of individuals in affected populations. [ABSTRACT FROM AUTHOR]

The phenolic content of free and bound phenolic extracts from Lycopus lucidus Turcz. harvested from two sites (S1 and S2) at three different times (T1, T2 and T3) was determined by Folin-Ciocalteu method. The content of gallic acid, chlorogenic acid, caffeic acid and rosmarinic acid in the phenolic extracts was detected by HPLC. Meanwhile, the protective effect of polyphenolic extracts on ·OH mediated DNA oxidative damage was evaluated. The results revealed that the phenolic contents of free and bound phenolic extracts were in the range of 86.53~181.40 and 89.70~193.58 μg GAE/mg, respectively. Higher amount of caffeic acid was found in the bound phenolic extract and the content of S2 L. lucidus Turcz. was higher than that of S1. Where as higher amount of rosmarinic acid was observed in the free phenolic extract. Furthermore, the rosmarinic acid content in S2 L. lucidus Turcz. was higher than that of S1 at T1 and T3. On the contrary, lower rosmarinic acid content was detected in S2 L. lucidus Turcz. at T2. The contents of caffeic acid and rosmarinic acid varied greatly with the harvest sites. The percentage of DNA double helices of free (25~300 μg/mL) and bound phenolic extracts (3.125~50 μg/mL) were in the range of 1.81%~55.04% and 1.67%~70.83%, respectively. The DNA damage protective effect of bound phenolics was higher than that of free phenolics.

A high performance liquid chromatography-ultraviolet-visible detector-electrospray ionization-ion trap-time-of-flight-mass spectrometry-total antioxidant capacity determination (HPLC-UVD-ESI-IT-TOF-MS-TACD) new online technique was developed for efficient screening of potential antioxidant active components in Prunus persica flowers (PPF) from 4 origins. Through this online system, 46 compounds were initially identified, while 20 compounds with DPPH binding activity and 21 compounds with FRAP binding activity were detected. The antioxidant activities of 9 compounds obtained from the screening were then validated in DNA oxidative damage protection study. The results showed that this online system can cope well with the complexity of the samples. This also provides technical basis for rapid screening of antioxidant resources of PPF. In short, this study made the chemical composition of PPF more abundant and its potential antioxidant active compounds more explicit, which provided new ideas for the detection and development of natural antioxidants and provided scientific basis for PPF as functional food. [Display omitted] • A HPLC-UVD-ESI-IT-TOF-MS-TACD online system was established. • 46 compounds in P. persica flowers were identified, of which 34 were novel. • 21 potential antioxidant compounds of P. persica flowers were efficiently detected. • The activity of 9 compounds were validated by DNA damage protection experiment. • The antioxidant activity of P. persica flowers from 4 origins was compared. [ABSTRACT FROM AUTHOR]

8-hydroxydeoxyguanosine (8-OHdG) in human urine is a marker reflecting oxidative stress and DNA oxidative damage. People spend 80%-90% of their life indoors; therefore, indoor air quality is directly related to human health. In this paper, the urinary 8-OHdG levels were presented in populations grouped by different demographic characteristics, lifestyle, occupational exposure, and health status, and elucidated indoor pollutants affecting human urinary 8-OHdG level, such as pollutants from outdoor sources, smoking, indoor combustion and cooking fumes, the chemicals in interior decoration materials, and building foundation soils. The article aims to provide a theoretical basis for predicting the impact of indoor air pollution on human health (DNA oxidative damage and related diseases) by measuring the concentration of 8-OHdG in human urine.

Abstract Background Most plants encounter water stress at one or more different stages of their life cycle. The maintenance of genetic stability is the integral component of desiccation tolerance that defines the storage ability and long-term survival of seeds. Embryonic axes of desiccation-sensitive recalcitrant seeds of Acer pseudoplatnus L. were used to investigate the genotoxic effect of desiccation. Alkaline single-cell gel electrophoresis (comet assay) methodology was optimized and used to provide unique insights into the onset and repair of DNA strand breaks and 8-oxo-7,8-dihydroguanine (8-oxoG) formation during progressive steps of desiccation and rehydration. Results The loss of DNA integrity and impairment of damage repair were significant predictors of the viability of embryonic axes. In contrast to the comet assay, automated electrophoresis failed to detect changes in DNA integrity resulting from desiccation. Notably, no significant correlation was observed between hydroxyl radical (٠OH) production and 8-oxoG formation, although the former is regarded to play a major role in guanine oxidation. Conclusions The high-throughput comet assay represents a sensitive tool for monitoring discrete changes in DNA integrity and assessing the viability status in plant germplasm processed for long-term storage.

This study aims to determine whether exposure to non-ionizing radiofrequency fields could induce an adaptive response (AR) in adult mice and to reveal potential molecular mechanisms triggered by RF-induced AR. The study was performed on 24 adult male Swiss-Albino mice. The average mass of the mice was 37 g. Four groups of adult mice, each consisting of 6, were formed. The radiofrequency group (R) and the adaptive response group (RB) were exposed to 900 MHz of global system for mobile communications (GSM) signal at 0.339 W/kg (1 g average specific absorption rate) 4 h/day for 7 days, while the control group (C) and the bleomycin group (B) were not exposed. 20 minutes after the last radiofrequency field (RF) exposure, the mice in the B and RB groups were injected intraperitoneal (ip) bleomycin (BLM), 37.5 mg/kg. All the animals were sacrificed 30 minutes after the BLM injection. Oxidative damage and antioxidant mechanism were subsequently investigated in the blood samples. Changes in the expression of the genes involved in DNA repair were detected in the liver tissue. TUNEL method was used to determine the apoptosis developed by DNA fragmentation in the liver tissue. The RB group, which produced an adaptive response, was compared with the control group. According to the results, the increase of reactive oxygen species (ROS) in the RB group may have played an important role in triggering the adaptive response and producing the required minimum stress level. Furthermore, tumor suppressor 53(p53), oxo guanine DNA glycosylase (OGG-1) levels responsible for DNA repair mechanism genes expression were increased in conjunction with the increase in ROS. The change in the poly (ADP-ribose) polymerase 1 (PARP-1) and glutathione peroxidase 1 (GPx-1) gene expression were not statistically significant. The antioxidant enzyme levels of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were decreased in the group with adaptive response. According to the data obtained from terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis, apoptosis was decreased in the RB group due to the decrease in cell death, which might have resulted from an increase in gene expression responsible for DNA repair mechanisms. The results of our study show that exposure to RF radiation may create a protective reaction against the bleomycin. The minimal oxidative stress due to the RF exposure leads to an adaptive response in the genes that play a role in the DNA repair mechanism and enzymes, enabling the survival of the cell. [ABSTRACT FROM AUTHOR]

The genotoxicity of nanomaterials has attracted great attention in recent years. As a possible occupational carcinogen, the genotoxic effects and underlying mechanisms of titanium dioxide nanoparticles (TiO2 NPs) have been of particular concern. In this study, the effect of TiO2 NPs (0, 25, 50 and 100 µg/mL) on DNA damage and the role of oxidative stress were investigated using human bronchial epithelial cells (BEAS-2B) as an in vitro model. After detailed characterization, the cytotoxicity of TiO2 NPs was detected. Through transmission electron microscopy (TEM), we found that TiO2 NPs entered the cytoplasm but did not penetrate deep into the nucleus of cells. The intracellular levels of reactive oxygen species (ROS) significantly increased in a dose-dependent manner and the ratios of GSH/GSSG also significantly decreased. The results of the normal comet assay were negative, while the Fpg-modified comet assay that specifically detected DNA oxidative damage was positive. Meanwhile, N-acetyl-L-cysteine (NAC) intervention inhibited the oxidative stress and genotoxicity induced by TiO2 NPs. Therefore, it was suggested that TiO2 NPs could induce cytotoxicity, oxidative stress and DNA oxidative damage in BEAS-2B cells. DNA oxidative damage may be a more sensitive genetic endpoint to detect the genotoxicity of TiO2 NPs. [ABSTRACT FROM AUTHOR]

DNA adducts are widely recognized as biomarkers of exposure to environmental carcinogens and associated health effects in toxicological and epidemiological studies. This study presents a targeted and sensitive method for comprehensive DNA adductome analysis using ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (UHPLC-QqQ-MS/MS). The method was developed using calf thymus DNA, with careful optimization of mass spectrometric parameters, chromatographic separation conditions, and pretreatment methods. Ultimately, a targeted method was established for 41 DNA adducts, which showed good linearity (R2 ≥0.992), recovery (80.1–119.4 %), accuracy (81.3–117.8 %), and precision (relative standard deviation <14.2 %). The established method was employed to analyze DNA adducts in peripheral blood cells from pregnant women in Shanxi and Beijing. Up to 23 DNA adducts were successfully detected in samples of varying sizes. From 2 μg of maternal DNA samples, seven specific adducts were identified: 5-methyl-2'-deoxycytidine (5-MedC), 5-hydroxymethyl-2'-deoxycytidine (5-HmdC), N6-methyl-2'-deoxyadenosine (N6-MedA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 5-hydroxy-2'-deoxycytidine (5-OHdC), 1,N6-etheno-2'-deoxyadenosine (1,N6-εdA), and N2-methyl-2'-deoxyguanosine (N2-MedG). This study reveals that exposure to higher concentrations of ambient air pollutants may elevate the levels of DNA methylation and oxidative damage at different base sites, highlighting the application potential of DNA adducts as sensitive biomarkers of air pollution exposure. [Display omitted] • A targeted DNA adductome method was developed for the simultaneous determination of 41 DNA adducts. • Seven specific DNA adducts were identified from 2 μg of maternal DNA. • Air pollution exposure may increase DNA methylation and oxidative damage levels at various base sites. [ABSTRACT FROM AUTHOR]

Modifications of DNA nucleobases are present in all forms of life. The purpose of these modifications in eukaryotic cells, however, is not always clear. Although the role of 5-methylcytosine (m5C) in epigenetic regulation and the maintenance of stability in plant genomes is becoming better understood, knowledge pertaining to the origin and function of oxidized nucleobases is still scarce. The formation of 5-hydroxymetylcytosine (hm5C) in plant genomes is especially debatable. DNA modifications, functioning as regulatory factors or serving as DNA injury markers, may have an effect on DNA structure and the interaction of genomic DNA with proteins. Thus, these modifications can influence plant development and adaptation to environmental stress. Here, for the first time, the changes in DNA global levels of m5C, hm5C, and 8-oxo-7,8-dihydroguanine (8-oxoG) measured by ELISA have been documented in recalcitrant embryonic axes subjected to desiccation and accelerated aging. We demonstrated that tissue desiccation induces a similar trend in changes in the global level of hm5C and 8-oxoG, which may suggest that they both originate from the activity of reactive oxygen species (ROS). Our study supports the premise that m5C can serve as a marker of plant tissue viability whereas oxidized nucleobases, although indicating a cellular redox state, cannot. [ABSTRACT FROM AUTHOR]

Chromium (VI) is the most dangerous oxidation state among the stable forms of chromium. In this work, we evaluated the effect of exposing Mytilus galloprovincialis for 24 h to 1, 10, and 100 nM chromium (VI) on the properties of Protamine-like (PLs) and their gene levels in the gonads. Specifically, we analyzed, by AU-PAGE and SDS-PAGE, PLs extracted from unexposed and exposed mussels. In addition, via EMSA, we evaluated the ability of PLs to bind DNA and also verified their potential to protect DNA from oxidative damage. Finally, we assessed possible alterations in gonadal expression of mt10, hsp70, and genes encoding for PLs-II/PL-IV and PL-III. We found that for all experimental approaches the most relevant alterations occurred after exposure to 1 nM Cr(VI). In particular, a comigration of PL-II with PL-III was observed by SDS-PAGE; and a reduced ability of PLs to bind and protect DNA from oxidative damage was recorded. This dose of chromium (VI) exposure was also the one that produced the greatest alterations in the expression of both mt10 and PL-II/PL-IV encoding genes. All of these changes suggest that this dose of chromium (VI) exposure could affect the reproductive health of Mytilus galloprovincialis. [ABSTRACT FROM AUTHOR]

In these studies, we investigated the antioxidant activity of three ruthenium cyclopentadienyl complexes bearing different imidato ligands: (η5-cyclopentadienyl)Ru(CO)2-N-methoxysuccinimidato (1), (η5-cyclopentadienyl)Ru(CO)2-N-ethoxysuccinimidato (2), and (η5-cyclopentadienyl)Ru(CO)2-N-phthalimidato (3). We studied the effects of ruthenium complexes 1–3 at a low concentration of 50 µM on the viability and the cell cycle of peripheral blood mononuclear cells (PBMCs) and HL-60 leukemic cells exposed to oxidative stress induced by hydrogen peroxide (H2O2). Moreover, we examined the influence of these complexes on DNA oxidative damage, the level of reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. We have observed that ruthenium complexes 1–3 increase the viability of both normal and cancer cells decreased by H2O2 and also alter the HL-60 cell cycle arrested by H2O2 in the sub-G1 phase. In addition, we have shown that ruthenium complexes reduce the levels of ROS and oxidative DNA damage in both cell types. They also restore SOD activity reduced by H2O2. Our results indicate that ruthenium complexes 1–3 bearing succinimidato and phthalimidato ligands have antioxidant activity without cytotoxic effect at low concentrations. For this reason, the ruthenium complexes studied by us should be considered interesting molecules with clinical potential that require further detailed research. [ABSTRACT FROM AUTHOR]

Tackling microbial resistance requires continuous efforts for the development of new molecules with novel mechanisms of action and potent antimicrobial activity. Our group has previously identified metal-based compounds, [Ag(1,10-phenanthroline-5,6-dione)2]ClO4 (Ag-phendione) and [Cu(1,10-phenanthroline-5,6-dione)3](ClO4)2.4H2O (Cu-phendione), with efficient antimicrobial action against multidrug-resistant species. Herein, we investigated the ability of Ag-phendione and Cu-phendione to bind with double-stranded DNA using a combination of in silico and in vitro approaches. Molecular docking revealed that both phendione derivatives can interact with the DNA by hydrogen bonding, hydrophobic and electrostatic interactions. Cu-phendione exhibited the highest binding affinity to either major (− 7.9 kcal/mol) or minor (− 7.2 kcal/mol) DNA grooves. In vitro competitive quenching assays involving duplex DNA with Hoechst 33258 or ethidium bromide demonstrated that Ag-phendione and Cu-phendione preferentially bind DNA in the minor grooves. The competitive ethidium bromide displacement technique revealed Cu-phendione has a higher binding affinity to DNA (Kapp = 2.55 × 106 M−1) than Ag-phendione (Kapp = 2.79 × 105 M−1) and phendione (Kapp = 1.33 × 105 M−1). Cu-phendione induced topoisomerase I-mediated DNA relaxation of supercoiled plasmid DNA. Moreover, Cu-phendione was able to induce oxidative DNA injuries with the addition of free radical scavengers inhibiting DNA damage. Ag-phendione and Cu-phendione avidly displaced propidium iodide bound to DNA in permeabilized Pseudomonas aeruginosa cells in a dose-dependent manner as judged by flow cytometry. The treatment of P. aeruginosa with bactericidal concentrations of Cu-phendione (15 µM) induced DNA fragmentation as visualized by either agarose gel or TUNEL assays. Altogether, these results highlight a possible novel DNA-targeted mechanism by which phendione-containing complexes, in part, elicit toxicity toward the multidrug-resistant pathogen P. aeruginosa. [ABSTRACT FROM AUTHOR]

Bisphenol A (BPA) is an industrial chemical used as an additive in conventional point-of-sale thermal paper receipts, in the production of many polycarbonate plastics, and epoxy resins lignin for food. BPA is xenoestrogen, a foreign compound that is not naturally produced in living organisms, but which acts similarly to natural 17-ß estradiol (natural estrogen). Due to its weak estrogenic activities, BPA exposure may influence multiple endocrine-related pathway, and is associated with prostate and breast cancer, neurobehavioral deficits, heart disease, and obesity. Furthermore, BPA may act as a DNA methylation agent and cause altered gene expression in the brain. Human exposure to bisphenol A is a matter of controversy. This review shows a potential risks in workplace resulting from contact with bisphenol A. The work presents the contribution of BPA exposure levels via dermal contact and the relationship between BPA exposure level and oxidative DNA damage.

Background: Most plants encounter water stress at one or more different stages of their life cycle. The maintenance of genetic stability is the integral component of desiccation tolerance that defines the storage ability and long-term survival of seeds. Embryonic axes of desiccation-sensitive recalcitrant seeds of Acer pseudoplatnus L. were used to investigate the genotoxic effect of desiccation. Alkaline single-cell gel electrophoresis (comet assay) methodology was optimized and used to provide unique insights into the onset and repair of DNA strand breaks and 8-oxo-7,8-dihydroguanine (8-oxoG) formation during progressive steps of desiccation and rehydration. Results: The loss of DNA integrity and impairment of damage repair were significant predictors of the viability of embryonic axes. In contrast to the comet assay, automated electrophoresis failed to detect changes in DNA integrity resulting from desiccation. Notably, no significant correlation was observed between hydroxyl radical (٠OH) production and 8-oxoG formation, although the former is regarded to play a major role in guanine oxidation. Conclusions: The high-throughput comet assay represents a sensitive tool for monitoring discrete changes in DNA integrity and assessing the viability status in plant germplasm processed for long-term storage. [ABSTRACT FROM AUTHOR]

Abstract Background High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2′-deoxyguanosine (8-OHdG), a product of oxidative damage to 2′-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear. Methods A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. Results A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437–2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482–3.005) using Cox multivariate analyses. Conclusions This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.

Bisphenol A (BPA) is a major component of the most commonly used plastic products, such as disposable plastics, Tetra Paks, cans, sport protective equipment, or medical devices. Due to the accumulation of excessive amounts of plastic waste and the subsequent release of BPA into the environment, BPA is classified as a pollutant that is undesirable in the environment. To date, the most interesting finding is the ability of BPA to act as an endocrine disrupting compound due to its binding to estrogen receptors (ERs), and adverse physiological effects on living organisms may result from this action. Since evidence of the potential pro-oxidizing effects of BPA has accumulated over the last years, herein, we focus on the detection of oxidative stress and its origin following BPA exposure using pulsed-field gel electrophoresis, flow cytometry, fluorescent microscopy, and Western blot analysis. Saccharomyces cerevisiae cells served as a model system, as these cells lack ERs allowing us to dissect the ER-dependent and -independent effects of BPA. Our data show that high concentrations of BPA affect cell survival and cause increased intracellular oxidation in yeast, which is primarily generated in the mitochondrion. However, an acute BPA exposure does not lead to significant oxidative damage to DNA or proteins. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effect of eight weeks of aerobic training and training in water on oxidative stress indices and total antioxidant capacity in elderly women. A total of 45 volunteered women participate as a subject for the study. Subjects were randomly divided into three groups; Aerobic (15 subjects), Training in water (15 subjects) and Control (15 subjects). Before the beginning of the training period, 8-OHdG, 8-isoprostane and total antioxidant capacity were measured. Both training groups were performed aerobic exercise on lane and water for three sessions per week with 65–75 percent of maximum heart rate. At the end of the training period, again, the blood sampling was repeated. For the statically analysis, ANOVA test was used, and for significant variables Bunferroni post hoc was used. Results showed significant difference in the level of OHdG, 8-isoprostane and total antioxidant capacity between trained groups and the control group after the training period (P < 0.004, P < 0.002, respectively). There was no significant difference between training groups in all variables (P < 0.734). In general, the results showed that moderate aerobic exercise in water and land can decrease oxidative stress induced damage and increase antioxidant system capacity. [ABSTRACT FROM AUTHOR]

Nowadays, there have been attempts to use phytochemicals in fruits to reduce the risk of suffering a given sickness. In this work, we studied the potential effects of mango (cultivar "Nam Dok Mai") and banana (cultivar "Khai") to attenuate DNA oxidative damage in MCF‐10A cells induced by 4‐hydroxyestradiol (4‐OHE2). The effects of mango extract (MNE) and banana extract (BKE) were comparable with three carotenoid compounds, β‐carotene, lycopene, and lutein. The oxidative‐induced DNA damage was evaluated by 8‐hydroxy‐2‐deoxyguanosine (8‐OHdG) reduction. 4‐OHE2‐induced DNA oxidative damage in MCF‐10A cells showed a decrease in 8‐OHdG formation when treated with MNE and BKE. Both fruit extracts also enabled the regaining production of Phase II detoxifying (GSTs and NQO1) and antioxidant (SOD, GPx, and CAT) enzymes during 4‐OHE2‐induced DNA oxidative damage in the MCF‐10A cells when compared with the untreated control. These results indicate that MNE and BKE can exert potential mitigating effects against 4‐OHE2‐induced DNA oxidative damage in MCF‐10A cells by enhancing the activities of detoxifying and antioxidant enzyme. Practical applications: Long‐term exposure to estrogen increases the risk of sickness since oxidative stress via the estrogen pathway, leading to DNA damage. This study indicated that mango (cultivar "Nam Dok Mai") extract contains β‐carotene and lycopene, while banana (cultivar "Khai") extract contains β‐carotene and lutein, which act as natural antioxidants. Both fruit extracts have preventive properties against oxidative DNA damage and are potentially good supplements for women taking E2 between HRT. [ABSTRACT FROM AUTHOR]

Background: DNA oxidative damage is a marker of increased oxidative stress activity. Elevated DNA oxidative damage has been associated with major depressive disorder in young adults, but there is no information about DNA oxidative damage in late-life depression. This study aims to evaluate whether older adults with late-life depression (LLD) has increased DNA oxidative damage compared to healthy older adults.Methods: We included 92 participants (57 with LLD [73.2 ± 7.7 years-old] and 35 non-depressed subjects (Controls) [70.5 ± 7.4 years-old]). We analyzed the plasma 8‑hydroxy-2'-deoxyguanosine (8-oxo-dG), a marker of DNA oxidation, using a commercially-available ELISA assay.Results: LLD participants had significantly higher 8-oxo-DG levels compared to controls (P<0.001). 8-oxo-dG levels were significantly correlated with depressive symptoms as assessed by the Hamilton Depression Rating Scale (rho=0.34, p<0.001). The plasma levels of 8-OHdG were not significantly correlated with other clinical, neurocognitive, and demographic variables.Limitations: Our current results are limited by the relatively small sample size, cross-sectional design, and the recruitment of participants in tertiary center for assessment and treatment of LLD.Conclusions: Older adults with LLD have increased DNA oxidative damage. Our findings provide additional evidence for elevated oxidative stress activity in LLD and the possible activation of age-related biological pathways and enhanced biological aging changes in LLD. [ABSTRACT FROM AUTHOR]

Diesel engine exhaust (DEE) is a complex mixture of toxic gases, halogenated aromatic hydrocarbons, alkyl polycyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons, benzene derivatives, metals and diesel exhaust particles (DEPs) generated from the incomplete combustion of diesel fuel. Many of the compounds in this mixture can cause oxidative damage to DNA and are considered carcinogenic for humans. Further, chronic DEE exposure increases risks of cardiovascular and pulmonary diseases. Despite these pervasive health risks, there is limited and inconsistent information regarding genetic factors conferring susceptibility or resistance to DEE genotoxicity. The present study evaluated the effects of polymorphisms in two base excision repair (BER) genes (OGG1 Ser326Cys and XRCC1 Arg280His), one homologous recombination (HRR) gene (XRCC3 Thr241Met) and two xenobiotic metabolism genes (GSTM1 and GSTT1) on the genotoxicity profiles among 123 mechanics exposed to workplace DEE. Polymorphisms were determined by PCR-RFLP. In comet assay, individuals with the GSTT1 null genotype demonstrated significantly greater % tail DNA in lymphocytes than those with non-null genotype. In contrast, these null individuals exhibited significantly lower frequencies of binucleated (BN) cells and nuclear buds (NBUDs) in buccal cells than non-null individuals. Heterozygous hOGG1 326 individuals (hOGG1 326 Ser/Cys) exhibited higher buccal cell NBUD frequency than hOGG1 326 Ser/Ser individuals. Individuals carrying the XRCC3 241 Met/Met polymorphism also showed significantly higher buccal cell NBUD frequencies than those carrying the XRCC3 241 Thr/Thr polymorphism. We found a high flow of particulate matter with a diameter of < 2.5 μm (PM2.5) in the workplace. The most abundant metals in DEPs were iron, copper, silicon and manganese as detected by transmission electron microscopy–energy-dispersive X-ray spectroscopy (TEM-EDX). Scanning electron microscopy (SEM-EDS) revealed particles with diameters smaller than PM2.5, including nanoparticles forming aggregates and agglomerates. Our results demonstrate the genotoxic effects of DEE and the critical influence of genetic susceptibility conferred by DNA repair and metabolic gene polymorphisms that shed light into the understanding of underlying mechanisms. [ABSTRACT FROM AUTHOR]

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Xuena Zhu,1 Mehenur Sarwar,1 Qiaoli Yue,2 Chunying Chen,3 Chen-Zhong Li1,4 1Nanobioengineering/Bioelectronics Laboratory, Department of Biomedical Engineering, Florida International University, Miami, FL, USA; 2Department of Chemistry, College of Chemistry and Chemical Engineering, Liao Chen University, Shandong, 3CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing, 4Key Laboratory of Analytical Chemistry for Life Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, People’s Republic of China Abstract: Non-glucose biomarker-DNA oxidative damage biomarker 8-hydroxy-2'-deoxyguanosine (8-OHdG) has been successfully detected using a smartphone-enabled glucose meter. Through a series of immune reactions and enzymatic reactions on a solid lateral flow platform, 8-OHdG concentration has been converted to a relative amount of glucose, and therefore can be detected by conventional glucose meter directly. The device was able to detect 8-OHdG concentrations in phosphate buffer saline as low as 1.73 ng mL-1 with a dynamic range of 1–200 ng mL-1. Considering the inherent advantages of the personal glucose meter, the demonstration of this device, therefore, should provide new opportunities for the monitoring of a wide range of biomarkers and various target analytes in connection with different molecular recognition events. Keywords: 8-OHdG, immunostrip, point-of-care, POCTs, biosensor, DNA oxidative damage

Background: Khat chewing is culturally endemic in the Southern areas of Saudi Arabia. Many health-related issues such as the incidence of carcinogenicity and comorbidities associated with the chewing of khat have been reported earlier. Objectives: Mainly, the objective of the study was to assess the risk of genotoxicity caused due to oxidative stress that may result from khat chewing among chronic chewers from Jazan Province of Saudi Arabia. Materials and Methods: Hundred and twenty-two adult males were recruited after signing informed consent. Ninety participants were chronic khat chewers (CKCs), while the control group consisted of 32 non-chewers of matched age and gender for the study group. A blood sample was collected from all participants and kept at 4°C until the time of assay. The activity of superoxide dismutase (SOD) and glutathione reductase (GR) were estimated in erythrocyte lysate as well as 8-hydroxydeoxyguanosine (8-OHdG) level in plasma. Results: There is a decreased SOD activity, which might be due to an increase in the endogenous production of reactive oxygen species resulted from the increase in lipid hydroperoxides. Furthermore, the significant elevation in GR activity was observed, reflecting the presence of highly toxic compounds. The 8-OHdG levels were higher in khat chewers group in comparison to the control, but this increase was statistically insignificant. Conclusion: CKCs will be at considerable risk of oxidative stress as a result of a significant reduction in antioxidant enzymes. This would be a good reason for them to quit chewing khat for health benefits. [ABSTRACT FROM AUTHOR]

Background: High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear.Methods: A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value.Results: A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses.Conclusions: This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research. [ABSTRACT FROM AUTHOR]

Endogenous cell metabolism and chemical reactions can induce oxidative DNA damage, which is involved in the development of different diseases. In this work, a label-free electrochemiluminescence (ECL) assay was proposed for the sensitive detection of oxidative DNA damage in an assembled DNA film. We employed the formamidopyrimidine-DNA glycosylase (Fpg) to convert DNA oxidative nucleobases to strand break, allowing to detect the DNA damage inducing minimal change to the helical structure of DNA. A "light-switch" DNA intercalator, [Ru(bpy) 2 (dppz)]2+ (bpy = 2, 2 ′ -bipyridine, dppz = dipyrido[3, 2-a:2 ′ , 3 ′ -c]phenazine) was introduced as an ECL signal reporter to detect the DNA strand breaks. The damaged DNA film on the reduced graphene oxide and gold nanoparticles (r-GO@Au) modified ITO electrode bound less ECL indicator than the intact film and accompanied by a drop in ECL intensity, which were also confirmed by gel electrophoresis and fluorescence measurements. As a result, a Fe2+-mediated Fenton reaction with as low as 10 nM Fe2+ and 40 nM H 2 O 2 induced DNA damage can be detected, 100-fold lower than the concentration measured without Fpg. To demonstrate its universality, the successful detection of DNA damage induced by Rose Bengal under irradiation was also achieved. The proposed strategy shows its potential practicality for the sensitive and rapid assessment of the genotoxicity of environmental pollutants. Image 1 [ABSTRACT FROM AUTHOR]

Abstract In this work, an electrochemical method for sensitive analysis of 8-hydroxy-2′-deoxyguanosine, a key biomarker that is widely used to study oxidative injury-related diseases, is proposed based on exonuclease-mediated functional nucleic acid. In the design, exonuclease can not only distinguish the existence of target, but also suppress the background noise, thus the sensitivity can be enhanced. Moreover, DNAzyme designed in the functional nucleic acid can further improve the sensitivity of the analysis during signal generation process. Therefore, exonuclease-mediated functional nucleic acid may ensure high sensitivity of the assay. Further studies reveal that the detection of 8-hydroxy-2′-deoxyguanosine can be achieved with a linearity from 0.01 nM to 7.0 μM and a detection limit of 6.82 pM. The new method has also been successfully applied to the determination of 8-OHdG in urine with good results, indicating its great potential for practical use. Graphical abstract fx1 Highlights • A novel electrochemical biosensor for 8-OHdG detection has been developed. • The combination of aptamer and DNAzyme ensures the high selectivity and sensitivity of the assay. • The background signal is reduces by exonuclease. • The biosensor has been applied for urine samples detection with satisfactory results. [ABSTRACT FROM AUTHOR]

Abstract Diesel engine exhaust (DEE), which is the product of diesel combustion, is considered carcinogenic in humans. It comprises toxic gases, polycyclic aromatic hydrocarbons (PAHs) and particulate matter which can reach the pulmonary parenchyma and trigger various diseases, including cancer. The aim of the present study was to evaluate the potential cytotoxic and genotoxic effects of DEE exposure on peripheral blood and buccal epithelial cells in mechanics occupationally exposed to DEE. We recruited 120 exposed mechanics and 100 non-exposed control individuals. Significant differences were observed between the two groups in terms of percentage of tail DNA and damage index (DI) in the alkaline comet assay; levels of biomarkers by cytokinesis-block micronucleus cytome (CBMN-Cyt) assay; frequency of micronucleus (MN), nucleoplasmic bridge (NPB), nuclear bud (NBUD) and apoptotic cells (APOP) and levels of biomarkers for micronucleus, karyorrhexis (KRX), karyolysis (KRL) and condensed chromatin (CC) by the buccal micronucleus cytome (BM-Cyt) assay. A significant and positive correlation was found between the frequency of MN in lymphocytes and buccal cells in the exposed group. Also, there was a significant correlation between age and percentage of tail DNA and DI in the comet assay, APOP and MN in the CBMN-Cyt assay and NBUD and MN in the BM-Cyt assay. Additionally, we found a positive and significant correlation of MN frequency in lymphocytes and buccal cells and age and MN frequency in lymphocytes with the time of service (years). Regarding lifestyle-related factors, a significant correlation was observed between meat and vitamin consumption and NBUD formation on CBMN-Cyt and between meat consumption and MN formation on CBMN-Cyt. Of the BM-Cyt biomarkers, there was a correlation between alcohol consumption and NBUD formation and between binucleated cell (BN), pyknosis (PYC), CC and KRL occurrence and family cancer history. These results are the first data in Colombia on the cytotoxic and genotoxic effects induced by continuous exposure to DEE and thus showed the usefulness of biomarkers of the comet, CBMN-Cyt and BM-Cyt assays for human biomonitoring and evaluation of cancer risk in the exposed populations. Graphical abstract fx1 Highlights • Significant differences in biomarkers evaluated between exposed and control group. • A significant correlation between age and percentage tail DNA and DI in comet assay. • A significant correlation between age and APOP and MN in the CBMN-Cyt assay. • A significant correlation between age and NBUD and MN in the BM-Cyt assay. • A significant correlation between meat consumption and MN occurrence on CBMN-Cyt. [ABSTRACT FROM AUTHOR]

Abstract Pulmonary exposure to silver nanoparticles (AgNPs) revealed the potential of nanoparticles to cause pulmonary toxicity, cross the alveolar-capillary barrier, and distribute to remote organs. However, the mechanism underlying the effects of AgNPs on the cardiovascular system remains unclear. Hence, we investigated the cardiovascular mechanisms of pulmonary exposure to AgNPs (10 nm) with varying coatings [polyvinylpyrrolidone (PVP) and citrate (CT)], concentrations (0.05, 0.5 and 5 mg/kg body weight), and time points (1 and 7 days) in BALB/C mice. Silver ions (Ag+) were used as ionic control. Exposure to AgNPs induced lung inflammation. In heart, tumor necrosis factor α, interleukin 6, total antioxidants, reduced glutathione and 8-isoprostane significantly increased for both AgNPs. Moreover, AgNPs caused oxidative DNA damage and apoptosis in the heart. The plasma concentration of fibrinogen, plasminogen activation inhibitor-1 and brain natriuretic peptide were significantly increased for both coating AgNPs. Likewise, the prothrombin time and activated partial thromboplastin time were significantly decreased. Additionally, the PVP- and CT- AgNPs induced a significant dose-dependent increase in thrombotic occlusion time in cerebral microvessels at both time points. In vitro study on mice whole blood exhibited significant platelet aggregation for both particle types. Compared with AgNPs, Ag+ increased thrombogenicity and markers of oxidative stress, but did not induce either DNA damage or apoptosis in the heart. In conclusion, pulmonary exposure to AgNPs caused cardiac oxidative stress, DNA damage and apoptosis, alteration of coagulation markers and thrombosis. Our findings provide a novel mechanistic insight into the cardiovascular pathophysiological effects of lung exposure to AgNPs. Highlights • Cardiovascular pathophysiological effects of lung exposure to AgNPs were assessed. • AgNPs caused oxidative stress, DNA damage and apoptosis in the heart. • AgNPs induced prothrombotic events and alteration of coagulation markers. • Some dissimilarities were seen between the AgNPs effects and those of silver ions. [ABSTRACT FROM AUTHOR]

In this study, the inhibition of DNA oxidative damage and low-density lipoprotein (LDL) oxidation of royal jelly protein (RJP) hydrolysates obtained from two commercial proteases were investigated. The results showed that the inhibition of DNA oxidative damage induced by the Fenton reaction, RJP, RJPs hydrolyzed by alcalase (RJP-A), RJPs hydrolyzed by flavourzyme (RPJ-F) and RJP two-stage hydrolysates (RPJ-AF) all had the effect of inhibiting deoxyribose oxidative damage. The inhibition effect of RJP, RJP-A, RJP-F and RJP-AF (1.0 mg/mL) were 47.06%, 33.70%, 24.19% and 43.09%, respectively. In addition, studies have also found that both RJP and RJP hydrolysates can reduce the production of 8-OH-2′-dG and the order of its inhibitory ability is RJP-AF ≒ RJP-A > RJP-F > RJP. The inhibition of DNA damage induced by bleomycin-Fe3+/ascorbic acid (Asc) with the addition of RJP, RJP-A, RPJ-F and RPJ-AF were 17.16%, 30.88%, 25.00% and 37.25%, respectively. The results of LDL oxidation inhibition showed that RJP-AF (1 mg/mL) not only had the most effective inhibitory Cu2+-induced LDL oxidation to produce a thiobarbituric acid reactive substance (TBARS) but also extended the lag time of conjugated diene formation to 300 min, which was 3.3 times that of the control group.

Diabetes patients often suffer chronic vascular complications resulting from endothelial dysfunction, smooth muscle cell (SMC) proliferation, inflammation and disturbed oxidative balance. Empagliflozin is one of three approved sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes mellitus. was to determine the protective and repairing effect of EMPA in a model of vascular endothelial and SMC damage with 25-hydroxycholesterol (25-OHC). Human umbilical vascular endothelial cells (HUVECs) and SMCs were treated with compounds which induce DNA single-strand breaks (SSBs) and subjected to comet assay. Oxidative DNA damage was detected using endonuclease III (Nth) or human 8 oxoguanine DNA glycosylase (hOOG1). Reactive oxygen species (ROS) formation was determined by the fluorescence of a 6-carboxy-2′,7′-dichlorodihydrofluoresce probe in diacetate (H 2 DCFDA). 25-OHC-stimulated SMCs showed greater resistance to ROS generation and DNA damage compared to HUVECs. In both experimental models, EMPA treatment was associated with lower ROS production and DNA damage, including oxidative damage to purines and pyrimidines. This effect was not dose-dependent. EMPA was found to counteract this DNA damage by inhibiting ROS production. It appears that the EMPA induced indirect repair of DNA by inhibiting ROS production. [Display omitted] • 25-OHC-stimulated SMCs showed greater resistance to ROS generation compared to HUVECs. • 25-OHC-stimulated SMCs showed greater resistance to DNA damage compared to HUVECs. • EMPA treatment was associated with lower oxidative damage to purines and pyrimidines. • EMPA induced indirect repair of DNA by inhibiting ROS production. [ABSTRACT FROM AUTHOR]

8-oxoguanine DNA glycosylase (OGG1) is the main DNA glycosylase responsible for the excision of 7,8-dihydro-8-oxoguanine (8-oxoG) from duplex DNA to initiate base excision repair. This glycosylase activity is relevant in many pathological conditions including cancer, inflammation, and neurodegenerative diseases. To have a better understanding of the role of OGG1, we previously reported TH5487, a potent active site inhibitor of OGG1. Here, we further investigate the consequences of inhibiting OGG1 with TH5487. TH5487 treatment induces accumulation of genomic 8-oxoG lesions. Furthermore, it impairs the chromatin binding of OGG1 and results in lower recruitment of OGG1 to regions of DNA damage. Inhibiting OGG1 with TH5487 interferes with OGG1′s incision activity, resulting in fewer DNA double-strand breaks in cells exposed to oxidative stress. This study validates TH5487 as a potent OGG1 inhibitor that prevents the repair of 8-oxoG and alters OGG1–chromatin dynamics and OGG1′s recruitment kinetics.

The reaction mechanism and kinetics for the abstraction of hydrogen and addition of hydroxyl radical (OH) to 2′-deoxycytidine have been studied using density functional theory at MX06-2X/6-311+G(d,p) level in aqueous solution. The optimized geometries, energies, and thermodynamic properties of all stationary points along the hydrogen abstraction reaction and the addition reaction pathways are calculated. The single-point energy calculations of the main pathways at CCSD(T)/6-31+G(d,p)//MX06-2X/6-311+G(d,p) level are performed. The rate constants and the branching ratios of different channels are evaluated using the canonical variational transition (CVT) state theory with small-curvature tunneling (SCT) correction in aqueous solution to simulate the biological system. The branching ratios of hydrogen abstraction from the C1′ site and the C5′ site and OH radical addition to the C5 site and the C6 site are 57.27% and 12.26% and 23.85% and 5.69%, respectively. The overall calculated rate constant is 4.47 × 109 dm3 mol−1 s−1 at 298 K which is in good agreement with experiments. The study could help better understand reactive oxygen species causing DNA oxidative damage. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS)-induced DNA damage occurs in heavy metal exposure, but the simultaneous effect on DNA repair is unknown. We investigated the influence of co-exposure of lead (Pb), cadmium (Cd), and mercury (Hg) on 8-hydroxydeoxyguanosine (8-OHdG) and human repair enzyme 8-oxoguanine DNA glycosylase (hOGG1) mRNA levels in exposed children to evaluate the imbalance of DNA damage and repair. Children within the age range of 3-6 years from a primitive electronic waste (e-waste) recycling town were chosen as participants to represent a heavy metal-exposed population. 8-OHdG in the children’s urine was assessed for heavy metal-induced oxidative effects, and the hOGG1 mRNA level in their blood represented the DNA repair ability of the children. Among the children surveyed, 88.14% (104/118) had a blood Pb level >5 μg/dL, 22.03% (26/118) had a blood Cd level >1 μg/dL, and 62.11% (59/95) had a blood Hg level >10 μg/dL. Having an e-waste workshop near the house was a risk factor contributing to high blood Pb (rs = 0.273, p < 0.01), while Cd and Hg exposure could have come from other contaminant sources. Preschool children of fathers who had a college or university education had significantly lower 8-OHdG levels (median 242.76 ng/g creatinine, range 154.62-407.79 ng/g creatinine) than did children of fathers who had less education (p = 0.035). However, we did not observe a significant difference in the mRNA expression levels of hOGG1 between the different variables. Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels (βQ2 = 0.362, 95% CI 0.111-0.542; βQ3 = 0.347, 95% CI 0.103-0.531; βQ4 = 0.314, 95% CI 0.087-0.557). Associations between blood Hg levels and 8-OHdG were less apparent. Compared with low levels of blood Hg (quartile 1), elevated blood Hg levels (quartile 2) were associated with higher 8-OHdG levels (βQ2 = 0.236, 95% CI 0.039-0.406). Compared with children having low lead exposure (quartile 1), the children with high Pb exposure (quartiles 2, 3, and 4) had significantly higher 8-OHdG levels. [ABSTRACT FROM AUTHOR]

Polycyclic aromatic hydrocarbons (PAHs) were assessed in sediments (n = 7) collected from the mouth of the Balsas River, Pacific Coast, Mexico. The total PAH levels ranged between 142.1 and 3944.07 μg kg−1 in the summer and 137.65–3967.38 μg kg−1 in the winter, probably reflecting the anthropogenic activities of the region. Calculation of the four analytical ratios of [Anthracene/(Anthracene + Phenanthrene)]: [Fluoranthene/(Fluoranthene + Pyrene)], [Fluoranthene/Pyrene: Fluoranthene/(Fluoranthene + Pyrene)], [Indeno [123- cd ]Pyrene/(Indeno [123- cd ]Pyrene + Benzo [ghi]Perylene)]: [Benzo [ a ]anthracene/(Benzo [ a ]Anthracene + Chrysene)], and [Anthracene/Phenanthrene]: [Fluoranthene/(Fluoranthene + Pyrene)] revealed a mixed PAH source, from petroleum and biomass combustion. Significant statistical correlations (r 2 = 0.90) between the 4 and 5 ringed PAHs denote that adsorption is the principal mechanism for accumulation in sedimentary archives. Ecotoxicological indices (Mean Effect Range Medium Quotient and Mean Probable Effect Level Quotient) indicated moderate pollution with adverse biological impacts on ambient benthonic organisms. The calculations of Toxicity Equivalent Quotient and Mutagen Equivalent Quotient values proposed that the region is highly polluted by mutagenic and carcinogenic PAH compounds. The genotoxic evaluation of Lutjanus guttatus (Spotted rose snapper) presented significant DNA damage and discrepancies in Ethoxyresorufin- O -Deethylase activity. Based on the toxicological and genotoxicological evaluation of PAHs in sediments, the region was observed to be largely impacted from biological damage. [Display omitted] • PAHs mainly sourced from petroleum and biomass combustion and ranged between 139.88 and 3955.73 μg kg−1. • Spotted rose snapper fish presented significant DNA damage due to high cPAHs exposure. • Moderate to high PAH pollution indicate adverse biological effects on the benthos. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate antioxidant ability of mangosteen shell and explore the non-enzymatic repair reaction and possible mechanism of xanthones in mangosteen shell. Methods: Mangosteen shell was extracted by methanol to obtain the extract of mangosteen shell. The extract was then determined by various antioxidant assays in vitro, including protection against DNA damage, •OH scavenging,DPPH• (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS+• (2,2′-azino-bis(3-ethylbenzo- thiazoline-6-sulfonic acid diammonium) scavenging, Cu2+-chelating, Fe2+-chelating and Fe3+ reducing assays. Results: Mangosteen shell extract increased dose-dependently its percentages in all assays. Its IC50 values were calculated as 727.85±2.21,176.94±19.25, 453.91±6.47, 84.60±2.47, 6.81±0.28, 1.55±0.10, 3.93±0.17, and 9.52±0.53μg/mL, respectively for DNA damage assay, •OH scavenging assay, Fe2+-Chelating assay, Cu2+-Chelating assay, DPPH• scavenging assay, ABTS+• scavenging assay, Fe3+ reducing assay and Cu2+ reducing assay. Conclusion: On the mechanistic analysis, it can be concluded that mangosteen shell can effectively protect against hydroxyl-induced DNA oxidative damage. The protective effect can be attributed to the xanthones. One approach for xanthones to protect against hydroxyl-induced DNA oxidative damage may be ROS scavenging. ROS scavenging may be mediated via metal-chelating, and direct radical-scavenging which is through donating hydrogen atom (H·) and electron (e). However, both donating hydrogen atom (H·) and electron (e) can result in the oxidation of xanthone to stable quinone form.

Human cytochrome CYP1A2 is one of the major hepatic cytochrome P450s involved in many drugs metabolism, and chemical carcinogens activation. The CYP1A2-dsDNA interaction in situ evaluation using a DNA-electrochemical biosensor and differential pulse voltammetry was investigated. A dsDNA-electrochemical biosensor showed that CYP1A2 interacted with dsDNA causing conformational changes in the double helix chain and DNA oxidative damage. A preferential interaction between the dsDNA guanosine residues and CYP1A2 was found, as free guanine and 8-oxoguanine, a DNA oxidative damage biomarker, oxidation peaks were detected. This was confirmed using guanine and adenine homopolynucleotides-electrochemical biosensors. The CYP1A2-dsDNA interaction and dsDNA conformation changes was also confirmed by UV-Vis spectrophotometry. [ABSTRACT FROM AUTHOR]

The electrochemical behaviour of the antitumor drug mitomycin C (MMC) was investigated on carbon paste electrode over a wide pH range and using voltammetric techniques. The MMC undergoes diffusion-controlled irreversible oxidation in two different processes, one pH-independent for 2.2 ˂ pH ˂ 4.5 and one pH-dependent for 4.5 ˂ pH ˂ 12.0, and does not involve the formation of any electroactive oxidation product. Upon incubation in different pH electrolytes, chemical degradation of MMC was electrochemically detected by the appearance of a new oxidation peak at a lower potential. The chemically degraded MMC undergoes an irreversible, pH-dependent oxidation for 3.4 ˂ pH ˂ 5.4, and its redox products are reversibly oxidised. The spontaneous degradation of MMC in aqueous solution was confirmed by UV–Vis spectrophotometry. Moreover, a multilayer dsDNA-electrochemical biosensor was used to evaluate the interaction between MMC and DNA. The results have clearly proven that MMC interacts and binds to dsDNA strands immobilized onto a glassy carbon electrode surface and its metabolite(s) cause oxidative damage to DNA. [ABSTRACT FROM AUTHOR]

Genomic DNA is prone to a large number of insults by a myriad of endogenous and exogenous agents. The base excision repair (BER) is the major mechanism used by cells for the removal of various DNA lesions spontaneously or environmentally induced and the maintenance of genome integrity. The presence of persistent DNA damage is not compatible with life, since abrogation of BER leads to early embryonic lethality in mice. There are several lines of evidences showing existence of a link between deficient BER, cancer proneness and ageing, thus illustrating the importance of this DNA repair pathway in human health. Although the enzymology of BER mechanisms has been largely elucidated using chemically defined DNA damage substrates and purified proteins, the complex interplay of BER with another vital process like transcription or when DNA is in its natural state ( i.e. wrapped in nucleosome and assembled in chromatin fiber is largely unexplored. Cells use chromatin remodeling factors to overcome the general repression associated with the nucleosomal organization. It is broadly accepted that energy-dependent nucleosome remodeling factors disrupt histones-DNA interactions at the expense of ATP hydrolysis to favor transcription as well as DNA repair. Importantly, unlike transcription, BER is not part of a regulated developmental process but represents a maintenance system that should be efficient anytime and anywhere in the genome. In this review we will discuss how BER can deal with chromatin organization to maintain genetic information. Emphasis will be placed on the following challenging question: how BER is initiated within chromatin? [ABSTRACT FROM AUTHOR]

Whey protein isolated from bovine colostrums collected on the second day postpartum was two-stage hydrolyzed by alcalase and flavourzyme. The whey hydrolysates were finally fractionated by ultrafiltration (UF) with a 10 kDa molecular weight (MW) cutoff membrane and subsequently used to evaluate the effect of whey protein hydrolysis on inhibition of DNA oxidative damage and low-density lipoprotein (LDL) oxidation in vitro. Results showed that whey hydrolysis exhibited not only higher inhibitory activities of oxidative damage of deoxyribose but also an inhibitory effect on the breakdown of supercoiled DNA into open circular DNA and linear DNA. The quantities of 8-hydroxy-2'-deoxyguanosine (8-OH-2'-dG) formed with the addition of whey hydrolysate protein, the hydrolysate fraction of MW >10 kDa, and the hydrolysate fraction of MW <10 kDa were 0.25, 0.06, and 0.09 μg/mL, respectively. The lag time of conjugated diene formation of the control sample, which was only combined with cupric ions and LDL, was 90 min. The samples added with the hydrolysate fractions exhibited higher inhibitory activity on LDL oxidation. The whey hydrolysate fractions extended the lag time of conjugated diene formation to 270 min. The lag time of the whey hydrolysate fractions was 3 times that of the control. [ABSTRACT FROM AUTHOR]

To clarify the substantial basis of the excellent antioxidant capacity of Agrimonia pilosa Ledeb. Fourteen flavonoids were isolated and identified from Agrimonia pilosa Ledeb, seven of which have notable DPPH radical scavenging activities, i.e., catechin, luteolin, quercetin, quercitrin, hyperoside, rutin, luteolin-7-O- -glucoside with IC50 values of 5.06, 7.29, 4.36, 7.12, 6.34, 6.36 and 8.12 μM, respectively. The DNA nicking assay showed that five flavonoids from Agrimonia pilosa Ledeb-taxifolin, catechin, hyperoside, quercitrin and rutin-have good protective activity against DNA oxidative damage. Further, we analyzed the bioactivity-structure relationship of these 14 flavonoids by applying quantum theory. According to their O-H bond dissociation enthalpy (BDE), C ring's spin density and stable molecular structure, the relationship between their structures and radical scavenging capacities was evaluated and clarified. We found that among flavonoid aglycones from Agrimonia pilosa Ledeb, the O-H BDE of quercetin is lowest with the values of 69.02 and the O-H BDE of apigenin is highest with the values of 79.77. It is interesting that the O-H BDE value of isovitexin (78.55) with glycoside at C-6 position is lower than that of its aglycone (79.77) and vitexin (99.20) with glycoside at C-8 position. Further analysis indicated that the glycosidation of flavonoids at C-6 in the A-ring makes a more uniform distribution of spin density and improves the stability of free radicals leading to the increase in antioxidant capacity. Flavonoids with good antioxidant capacity might contribute to the pharmacological effects of Agrimonia pilosa Ledeb. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT)-mediated antitumor immune response depends on oxidative stress intensity and subsequent immunogenic cell death (ICD) in tumor cells, yet the inherent antioxidant system restricts reactive oxygen species (ROS)-associated oxidative damage, which is highly correlated with the upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) and the downstream products, such as glutathione (GSH). Herein, to overcome this dilemma, we designed a versatile nanoadjuvant (RI@Z-P) to enhance the sensitivity of tumor cells to oxidative stress via Nrf2-specific small interfering RNA (siNrf2). The constructed RI@Z-P could significantly amplify photooxidative stress and achieve robust DNA oxidative damage, activating the stimulator of interferon genes (STING)-dependent immune-sensing to produce interferon-β (IFN-β). Additionally, RI@Z-P together with laser irradiation reinforced tumor immunogenicity by exposing or releasing damage-associated molecular patterns (DAMPs), showing the prominent adjuvant effect for promoting dendritic cell (DC) maturation and T-lymphocyte activation and even alleviating the immunosuppressive microenvironment to some extent. [ABSTRACT FROM AUTHOR]