Search

Environmental insults can lead to alteration in DNA methylation of specific genes. To address the role of altered DNA methylation in prediction of polycyclic aromatic hydrocarbons (PAHs) exposure-induced genetic damage, we recruited two populations, including diesel engine exhausts (low-level) and coke oven emissions (high-level) exposed subjects. The positive correlation was observed between the internal exposure marker (1-hydroxypyrene) and the extents of DNA damage (P 0.05). The methylation of representative genes, including TRIM36, RASSF1a, and MGMT in peripheral blood lymphocytes was quantitatively examined by bisulfite-pyrosequencing assay. The DNA methylation of these three genes in response to PAHs exposure were changed in a CpG-site-specific manner. The identified hot CpG site-specific methylation of three genes exhibited higher predictive power for DNA damage than the respective single genes in both populations. Furthermore, the dose-response relationship analysis revealed a nonlinear U-shape curve of TRIM36 or RASSF1a methylation in combined population, which led to determination of the threshold of health risk. Furthermore, we established a prediction model for genetic damage based on the unidirectional-alteration MGMT methylation levels. In conclusion, this study provides new insight into the application of multiple epi-biomarkers for health risk assessment upon PAHs exposure.

Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10-5 ) and a significant exposure-response relationship with 5MC (p = 7 × 10-4 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10-3 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites.

The potential threat of superfine carbon black (CB) particles to human health has received attention, but there are few human toxicological data available. The purpose of this study was to investigate the relationships between serum CC16 and SP-A with small airway related pulmonary functions in CB workers. Ninety-nine male CB packers and 115 non-CB-exposed healthy male workers were recruited. Serum CC16 and/or SP-A and pulmonary function tests were evaluated, and the relationship between them were also analyzed. To further assess pulmonary damage induced by CB particles in target organs, an animal inhalation exposure study was conducted. Male C57BL/6 mice were exposed to 15 and 30 mg/m3 CB for 6 h per day for 28 days. Levels of CC16 and SP-A were evaluated by ELISA and immunohistochemical staining (IHC). The results showed a 20% decreased in median CC16 and a 15% increase in median SP-A among CB-exposed workers. FEV1%, FEV/FVC, MMEF%, FEF25%, and FEF75% were also decreased in CB-exposed workers (P

Exposure to diesel engine exhaust (DEE) was associated with various adverse health effects including lung cancer. Particle size distribution and profiles of organic compounds in both particle and gas phases of DEE that could provide valuable insights into related health effects were measured in a diesel engine testing workshop. Concentrations of urinary 6 mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) in 137 DEE-exposed workers and 127 non-DEE-exposed workers were determined. Benchmark dose method was applied to estimate lower limit of benchmark dose (BMDL) of urinary OH-PAHs most specific to DEE exposure for previously reported cancer biomarkers. We found that 84.3% of diesel exhaust particles were ultrafine particles. Indeno[123-cd]pyrene and phenanthrene were the most abundant carcinogenic and noncarcinogenic PAHs in the particle phase of DEE, respectively. Principal component analysis demonstrated that urinary hydroxyphenanthrene (OHPhe) had highest loading value on principal component (PC) representative of DEE exposure and lowest loading value on PC representative of smoking status. BMDLs of urinary OHPhe from best-fitting models for cancer biomarkers including micronucleus and 1,N6-ethenodeoxyadenosine were 1.08 μg/g creatinine and 2.82 μg/g creatinine, respectively. These results provided basis for understanding DEE exposure induced health effects and potential threshold for regulating DEE levels in an occupational setting.

Background: Diesel engine exhaust (DEE) is classified as a Group 1 human carcinogen by the International Agency for Research on Cancer because of its carcinogenicity to the lung. However, the underlying molecular mechanisms of DEE carcinogenicity are not well understood. Methods: We previously conducted a cross-sectional molecular epidemiology study of diesel engine factory workers exposed to a wide range of DEE and unexposed comparable controls. Here, we carried out a pilot study of a representative subgroup of 19 exposed workers (total n = 54) and 19 unexposed controls (total n = 55). We measured serum level of 1238 targeted proteins using the SOMAScan assay (SOMALogic, Boulder, CA), which measures protein involved in a wide range of biological processes. We used linear regression to identify proteins associated with DEE (permutation p-value Results: Occupational exposure to DEE was significantly associated with altered levels of 22 serum proteins. Of these, 13 proteins (CXCL11, HAPLN1, FLT4, CD40LG, PES1, IGHE.IGK..IGL, TNFSF9, PGD, NAGK, CCL25, CCL4L1, PDXK, and PLA2G1B) showed a significant exposure-response relationship with EC (p-trend Conclusion: Results from our pilot study suggest that DEE exposure is associated with alteration of multiple proteins in the serum, which play a role in inflammation and immune regulation. Analysis of a larger sample size will be needed to confirm our findings. Citation Format: Mohammad L. Rahman, Yufei Dai, Roel Vermeulen, Wei Hu, Bryan Bassig, Eduard Drizik, Sean Corbett, Dianzhi Ren, Huawei Duan, Yong Niu, Jun Xu, Wei Fu, Kees Meliefste, Baosen Zhou, Xiaohui Zhang, Jufang Yang, Hanqiao Liu, Meng Ye, Gang Liu, Xiaowei Jia, Tao Meng, Ping Bin, Avrum Spira, Marc E. Lenburg, Debra Silverman, Nathaniel Rothman, Yuxin Zheng, Qing Lan. Proteomic analysis of serum in workers exposed to diesel engine exhaust [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 856.

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values

Trichloroethylene (TCE) -induced hypersensitivity syndrome (TIHS) is a potentially life-threatening disease. Several genetic susceptibility biomarkers have been found to be associated with TIHS, and this systematic prospective study has been conducted to evaluate the utility of these genetic susceptibility biomarkers in preventing the disease.The newly hired TCE-exposed workers were recruited from March 2009 to October 2010.Among 1651 workers, 158 (9.57%) were found to carry theProspective

Background Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental and occupational pollutants. To date, the effect and mechanism by which PAHs exposure impaired hematopoietic system remains unclear. Methods We examined the capability of PAHs to disrupt hematopoiesis in a study of 639 male participants in China by measuring complete blood counts (CBC) in 2013 and 2014. Gas chromatography–mass spectrometry (GC/MS) method was used to measure airborne levels of PAHs and benzene. We measured 1-hydroxypyrene (1-OHP), S-phenylmercapturic acid (SPMA) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urinary by ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS/MS) method. Results We found decreased dose−response of white blood cells, eosinophils, monocytes and lymphocytes with increased PAHs exposure in two consecutive years. We did not find association between benzene with CBC in our study. After stratification analysis by smoking status, the findings were highly consistent. White blood cells, monocytes and red blood cell counts were decreased in high urinary 8-OHdG group. Conclusions Our study showed that PAHs could impair the hematopoietic system independently, and oxidative stress might play an important role in potential hematotoxicity.

Coke oven emissions (COEs) are common particle pollutants in occupational environment and the major constituents of COEs are polycyclic aromatic hydrocarbons (PAHs). Previously, we identified aberrant methylation of the fms related tyrosine kinase 1 (FLT1) gene over the course of benzo(a)pyrene (BaP)-induced cell transformation via genome-wide methylation array. To quantify FLT1 methylation, we established a bisulfite pyrosequencing assay and examined the FLT1 hypermethylation in several human cancers. The results revealed that 70.0% (21/30 pairs) of lung cancers harbored hypermethylated FLT1 and concomitant suppression of gene expression compared to the adjacent tissues. This implies that FLT1 hypermethylation might play a role in malignant cell transformation. In addition, FLT1 hypermethylation and gene suppression appeared in primary human lymphocytes in a dose-response manner following COEs treatment. To explore whether FLT1 methylation is correlated with COEs exposure and DNA damage, we recruited 144 male subjects who had been exposed to high levels of COEs and 84 male control subjects. Notably, the FLT1 methylation in peripheral blood lymphocytes (PBLCs) of the COEs-exposed group (19.8 ± 3.2%) was enhanced by 17.9% compared to that of the control group (16.8 ± 2.8%) (P 0.001). The FLT1 methylation status was positively correlated with urinary 1-hydroxypyrene (1-OHP) levels, an internal exposure marker of PAHs (β = 0.029, 95% CI = 0.010-0.048, P = 0.003) and positively correlated with DNA damage (β

To clarify the effects of lung function following exposure to diesel engine exhaust (DEE), we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p

Diesel engine exhaust (DEE) was found to induce lipid peroxidation (LPO) in animal exposure studies. LPO is a class of oxidative stress and can be reflected by detecting the levels of its production, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and etheno-DNA adducts including 1,N(6)-etheno-2'-deoxyadenosine (ɛdA) and 3,N(4)-etheno-2'-deoxycytidine (ɛdC). However, the impact of DEE exposure on LPO has not been explored in humans. In this study, we evaluated urinary MDA, 4-HNE, ɛdA, and ɛdC levels as biomarkers of LPO among 108 workers with exclusive exposure to DEE and 109 non-DEE-exposed workers. Results showed that increased levels of urinary MDA and ɛdA were observed in subjects occupationally exposed to DEE before and after age, body mass index (BMI), smoking status, and alcohol use were adjusted (all p 0.001). There was a statistically significant relationship between the internal exposure dose (urinary ΣOH-PAHs) and MDA, 4-HNE, and ɛdA (all p 0.001). Furthermore, significant increased relations between urinary etheno-DNA adduct and MDA, 4-HNE were observed (all p 0.05). The findings of this study suggested that the level of LPO products (MDA and ɛdA) was increased in DEE-exposed workers, and urinary MDA and ɛdA might be feasible biomarkers for DEE exposure. LPO induced DNA damage might be involved and further motivated the genomic instability could be one of the pathogeneses of cancer induced by DEE-exposure. However, additional investigations should be performed to understand these observations.

Etheno-DNA adducts are biomarkers for assessing oxidative stress. In this study, the aim was to detect the level of etheno-DNA adducts and explore the relationship between the etheno-DNA adducts and genotoxicity biomarkers of the diesel engine exhaust (DEE)-exposed workers. We recruited 86 diesel engine testing workers with long-term exposure to DEE and 99 non-DEE-exposed workers. The urinary mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and etheno-DNA adducts (edA and edC) were detected by HPLC-MS/MS and UPLC-MS/MS, respectively. Genotoxicity biomarkers were also evaluated by comet assay and cytokinesis-block micronucleus assay. The results showed that urinary edA was significantly higher in the DEE-exposed workers (p

Background: Diesel engine exhaust (DEE) exposure causes lung cancer, but the molecular mechanisms by which this occurs are not well understood. Objectives: To assess transcriptomic alterations in nasal epithelium of DEE-exposed factory workers to better understand the cellular and molecular effects of DEE. Methods: Nasal epithelial brushings were obtained from 41 diesel engine factory workers exposed to relatively high levels of DEE (17.2–105.4 μg/m3), and 38 unexposed workers from factories without DEE exposure. mRNA was profiled for gene expression using Affymetrix microarrays. Linear modeling was used to identify differentially expressed genes associated with DEE exposure and interaction effects with current smoking status. Pathway enrichment among differentially expressed genes was assessed using EnrichR. Gene Set Enrichment Analysis (GSEA) was used to compare gene expression patterns between datasets. Results: 225 genes had expression associated with DEE exposure after adjusting for smoking status (FDR q

This study assesses the effects of long-term exposure to ambient air pollutants on inflammatory response and lung function. We selected 390 male coke oven workers with exposure to polycyclic aromatic hydrocarbons (PAHs) and fine particulate matter (PM

Introduction Diesel engine exhaust (DEE) is a known lung carcinogen in humans (IARC Group 1). However, the biological mechanism underlying this association is unclear. Given the suspected relationship between inflammation and lung carcinogenesis, we evaluated associations between DEE exposure and a multiplex panel of immune markers in workers exposed to DEE and unexposed workers in China. Methods A cross-sectional molecular epidemiology study was conducted among 54 workers exposed to DEE in a diesel engine testing facility, and 55 unexposed workers who were employed in separate factories. Repeated personal exposure measurements of elemental carbon (EC) were taken from workers before blood collection. Serum levels of immune markers were analysed using a Luminex bead-based assay. Linear regression was used to evaluate differences in marker concentrations between DEE exposed vs. unexposed workers, and to explore exposure-response trends with EC. Results Four markers were significantly associated with DEE exposure in analyses of exposed vs. unexposed workers (P-value Conclusions Recent evidence suggests that higher levels of CCL15/MIP-1D and CCL2/MCP-1, two markers in the CC chemokine subfamily that attract white blood cells to sites of inflammation, are associated with increased risk of lung cancer in Asian never-smoking women. Alterations in these markers in the same direction among workers exposed to DEE in our study may provide mechanistic insight into the relationship between DEE and lung carcinogenesis.

Diesel engine exhaust (DEE), a ubiquitous environmental pollutant, has been associated with adverse health effects. Revelation of cellular and molecular changes is critical for understanding environmental exposure-related diseases. Although the molecular-level effects of DEE exposure have been investigated, whether it is associated with aberrant changes at cellular level is largely unknown at the population level. In the present study, we measured urinary concentrations of 6 mono-hydroxylated PAHs (OH-PAHs) and cytotoxicity-related endpoints including apoptosis and necrosis frequencies, and nuclear division cytotoxicity index (NDCI) in peripheral blood lymphocytes (PBLs) of 79 DEE-exposed workers and 59 non-DEE-exposed workers. We found that DEE-exposed workers had significantly higher necrosis frequency and lower NDCI than did non-DEE-exposed workers (both p 0.001). In all study subjects and nonsmoking workers, urinary summed OH-PAHs was associated with increased necrosis frequency and reduced NDCI. In nonsmoking workers, an interquartile range increase in urinary summed OH-PAHs was associated with 105.03% increase in necrosis frequency and 8.70% decrease in NDCI. Taking advantage of the previous measure of micronucleus frequency, we observed that micronucleus frequency was positively correlated with apoptosis and necrosis frequencies (r = 0.277, p = 0.047 and r = 0.452, p = 0.001, respectively) and negatively correlated with NDCI (r = -0.477, p 0.001). In conclusion, our results suggested that DEE exposure was associated with increased necrosis frequency and further with reduced NDCI in PBLs, providing evidence of DEE exposure-induced cytotoxicity in humans.

To investigate the effect of occupational exposure to toluene diisocyanate (TDI) on the workers' health.A total of 76 workers exposed to TDI (exposure group) and 64 management staff members (control group) were selected from a factory as the study subjects. Area sampling was performed for the place with exposure to TDI according to the method in GBZ 159-2004 Specifications of air sampling for hazardous substances monitoring in the workplace, and gas chromatography was applied to measure the concentration of TDI in workplace air. The workers' personal information was collected with questionnaire, pulmonary ventilation function was determined with a portable spirometer, hematological parameters were analyzed by automatic blood analyzer and blood chemistry analyzer, and the indicators of oxidative damage and energy metabolism were measured by the reagent kit provided by Nanjing Jiancheng Bioengineering Institute. SPSS 17 software was applied for statistical analysis.The exposure group had significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second(FEV1.0), and FEV1.0/FVC ratio than the control group (P0.05). Compared with the control group, the exposure group had significantly higher red blood cell count, platelet distribution width, mean platelet volume, lymphocyte count, and neutrophil count(P0.01), and significantly lower activities of lactate dehydrogenase(LDH), superoxide dismutase, and succinodehydrogenase (SDH)(P0.01). In the exposure group, the length of exposure was negatively correlated with the activities of SDH and LDH in the serum (r=-0.319, P0.05; r=-0.239, P0.05), and the length of exposure was not found to be correlated with the activity of SOD and pulmonary function indices.TDI can induce inflammatory response and lung ventilation function impairment in workers exposed to TDI, as well as oxidative stress and imbalance of energy metabolism. Therefore, it can cause damage to workers' health, and protective measures should be enhanced.

The International Agency for Research on Cancer has classified carbon black (CB) as a possible (Group 2B) human carcinogen. Given that most CB manufacturing processes result in the emission of various types of chemicals, it is uncertain if the adverse health effects that have been observed in CB-exposed workers are related to CB specifically or are due to other exposures. To address this issue, we conducted a cross-sectional molecular epidemiology study in China of 106 male factory workers who were occupationally exposed to pure CB and 112 unexposed male workers frequency-matched by age and smoking status from the same geographic region. Repeated personal exposure measurements were taken in workers before biological sample collection. Peripheral blood from all workers was used for the complete blood cell count and lymphocyte subsets analysis. Compared to unexposed workers, eosinophil counts in workers exposed to CB were increased by 30.8% (P = 0.07) after adjusting for potential confounders. When stratified by smoking status, statistically significant differences in eosinophils between CB exposed and unexposed workers were only present among never smokers (P = 0.040). Smoking is associated with alterations in various cell counts; however, no significant interaction between CB exposure and smoking status for any cell counts was observed. Given that inflammation, characterized in part by elevated eosinophils in peripheral blood, may be associated with increased cancer risk, our findings provide new biologic insights into the potential relationship between CB exposure and lung carcinogenesis. Environ. Mol. Mutagen. 57:589-604, 2016. © 2016 Wiley Periodicals, Inc.

The purpose of this study was to address the association between cytokine expression and the hypersensitivity dermatitis induced by trichloroethylene (TCE) exposure. 28 TCE-induced hypersensitivity dermatitis patients, 22 TCE exposed workers and 22 non-exposed controls were enrolled in the study. The serum levels of interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α were analyzed using a magnetic colorbead-based multiplex assay. The patients showed significantly higher levels of serum IL-1β (p=0.033 and p=0.015), IL-6 (p

Coke oven workers are regularly exposed to polycyclic aromatic hydrocarbons (PAHs) and have a high risk for lung cancer. Limited evidence has demonstrated a direct link between exposure to PAHs and early genetic damage in exposed workers. The cytokinesis-block micronucleus (CBMN) cytome assay is a comprehensive system for measuring DNA damage and cytotoxicity. In the current study, we investigated different chromosomal damage endpoints including micronuclei (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs), in 141 PAH-exposed subjects and 66 unexposed controls. The frequencies of MN, NPBs and NBUDs were all significantly higher in PAH-exposed workers than in controls (2.4-, 5-, and 3-fold, respectively). We further classified the PAH-exposed workers into different PAHs exposure groups based on their work positions on the oven and their urinary 1-hydroxypyrene and found that the frequencies of NPBs and NBUDs increased with the increasing level of both external and internal PAHs exposure levels. Similar trend was not found for MN due to the reduced MN frequency in the highest PAHs exposure group compared with the second highest PAHs exposure group. Using principal component analysis, we confirmed that the frequencies of NPBs and NBUDs are more sensitive to reflect the external or internal levels of PAHs exposure. In PAH-exposed subjects, NPB and NBUD frequencies were influenced by gender and females have lower frequencies of NPB and NBUD. Taken together, our observations indicate that NPBs and NBUDs are more sensitive and reliable biomarkers for genetic damages induced by PAHs and could potentially be used for the biomonitoring of genotoxin-exposed populations.

Polycyclic aromatic hydrocarbons (PAH) in coke oven emissions could cause lung cancer in human. Individual's genotype of the metabolic enzymes and early biological changes were known to be associated with the susceptibility of cancer development. Knowledge of metabolic gene polymorphisms, which affect on the urinary 1-hydroxypyrene (1-OHP), could benefit us in understanding the interindividual difference in the mechanism of PAH-induced carcinogenesis. In this study, we investigated the association of aryl hydrocarbon receptor (AhR) gene polymorphisms and urinary 1-OHP. One hundred forty-seven workers exposed to PAH and 69 nonexposure workers were recruited. Seven tagging single nucleotide polymorphisms in AhR gene were selected by pariwise r2 method and minor allele frequency cutoff of 0.05 from Chinese genotype data in HapMap project. These seven tagging single nucleotide polymorphisms were genotyped by PCR-based methods. Multivariate analysis of covariance revealed that the levels of 1-OHP in PAH-exposed workers carrying genotype CT were lower than workers carrying wild genotype TT at loci rs10250822 and rs2282885 of AhR gene (P = 0.032 and 0.044, respectively). In PAH-exposed workers, the urinary 1-OHP levels showed a linear correlation (Ptrend = 0.041) with the genotypes at locus rs2282885, especially in low and moderate exposure groups. In contrast, no significant association was found between urinary 1-OHP level and AhR genotypes among nonexposed workers. Our findings indicated that polymorphisms of AhR gene were associated with the level of 1-OHP among PAH-exposed workers, suggesting that AhR-mediated signaling might contribute to individual susceptibility to PAH exposure. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1702–8)

Background Trichloroethylene (TCE) is used extensively as an industrial solvent and has been recognized as one of the major environmental pollutants. To date, > 200 cases of TCE-induced hypersensitivity dermatitis among exposed workers have been reported worldwide, and TCE exposure has become one of the critical occupational health issues in Asia. Objectives The study aimed to identify genetic susceptible biomarkers associated with the TCE-induced hypersensitivity dermatitis in genes located in the human leukocyte antigen (HLA) region. Methods From 1998 to 2006, 121 cases with TCE-induced hypersensitivity dermatitis and 142 tolerant controls were recruited into the population-based case–control study. We determined HLA alleles B, DRB1, DQA1, and DQB1, by sequence-based typing. p-Values were corrected for comparisons of multiple HLA alleles. In addition, we compared and analyzed the structure character of amino acid residues of HLA molecules found in participants. Results We obtained complete genotyping data of 113 cases and 142 controls. The allele HLA-B*1301 was present in 83 (73.5%) of 113 patients compared with 13 (9.2%) of 142 tolerant workers (odds ratio = 27.5; 95% confidence interval, 13.5–55.7; corrected p = 1.48 × 10−21). In addition, the HLA-B*44 alleles were present in 6.2% (7/113) of patients, but were absent in TCE-tolerant workers. Residue 95 shared by HLA-B*1301 and HLA-B*44 molecules formed a different pocket F than other residues. Conclusions The allele HLA-B*1301 is strongly associated with TCE-induced hypersensitivity dermatitis among exposed workers and might be used as a biomarker to predict high risk individuals to TCE.

The associations between several genetic polymorphisms of nucleotide excision repair genes (NER) and chromosome damage level were studied among 140 coke-oven workers exposed to a high level of polyaromatic hydrocarbons (PAHs) and 66 non-exposed workers. Seven polymorphisms with functional potential in five NER genes (ERCC1, ERCC2, ERCC4, ERCC5 and ERCC6) were genotyped in the 206 study subjects. Multivariate analysis of covariance revealed that coke-oven workers with the ERCC1 19007 CC genotype had significantly higher cytokinesis-block micronucleus frequency (CBMN) (10.5 +/- 6.8 per thousand) than those with CT (8.1 +/- 6.6 per thousand, p = 0.01) or TT (6.6 +/- 3.7-/ per thousand p = 0.05) or CT+TT genotypes (7.5 +/- 6.3 per thousand, p = 0.004). The ERCC6 A3368G polymorphism was also associated with CBMN frequency among coke-oven workers. Subjects with the AA genotype have a significantly higher CBMN frequency (10.0 +/- 6.9 per thousand) than those with AG (6.7 +/- 4.2 per thousand, p = 0.05) or AG+GG genotypes (6.6 +/- 4.1 per thousand, p = 0.02). Stratification analysis revealed the significant associations between ERCC1 C19007T and ERCC6 A3368G, and the CBMN frequencies were only found among older workers. In addition, a significant association between ERCC2 G23591A polymorphism and CBMN frequencies was also found among older coke-oven workers. The results suggest that polymorphisms of ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A are associated with the CBMN frequencies among coke-oven workers.

To systematically evaluate the environmental exposure information of coke oven workers, we investigated the concentration and size distribution characteristics of the particle matter (PM) in the top working area of coke oven.The aerodynamic particle sizer spectrometer was employed to collect the concentration and size distribution information of PM at a top working area. The PM was divided into PM ≤ 1.0 µm, 1.0 µmPM ≤ 2.5 µm, 2.5 µmPM ≤ 5.0 µm, 5.0 µmPM ≤ 10.0 µm and PM10.0 µm based on their aerodynamic diameters. The number concentration, surface area concentration, and mass concentration were analyzed between different groups. We also conducted the correlation analysis on these parameters among groups.We found the number and surface area concentration of top area particulate was negatively correlated with particle size, but mass concentration curve showed bimodal type with higher point at PM = 1.0 µm and PM = 5.0 µm. The average number concentration of total particulate matter in the top working area was 661.27 number/cm³, surface area concentration was 523.92 µm²/cm³, and mass concentration was 0.12 mg/m³. The most number of particulate matter is not more than 1 µm (PM(1.0)), and its number concentration and surface area concentration accounted for 96.85% and 67.01% of the total particles respectively. In the correlation analysis, different particle size correlated with the total particulate matter differently. And the characteristic parameters of PM2.5 cannot fully reflect the total information of particles.The main particulate matter pollutants in the top working area of coke oven is PM1.0, and it with PM(5.0) can account for a large proportion in the mass concentration of PM. It suggest that PM1.0 and PM(5.0) should be considered for occupational health surveillance on the particulate matter in the top area of coke oven.

Diesel engine exhaust (DEE) is a ubiquitous environmental pollutant and is carcinogenic to humans. To seek early and sensitive biomarkers for prediction of adverse health effects, we analysed the components of DEE particles, and examined the genetic and oxidative damages in DEE-exposed workers.101 male diesel engine testing workers who were constantly exposed to DEE and 106 matched controls were enrolled in the present study. The components of DEE were analysed, including fine particulate matter (PM2.5), element carbon (EC), nitrogen dioxide (NO2), sulfur dioxide (SO2) and polycyclic aromatic hydrocarbons (PAHs). Postshift urine samples were collected and analysed for 1-hydroxypyrene (1-OHP), an internal exposure marker for DEE. Levels of DNA strand breaks and oxidised purines, defined as formamidopyrimidine-DNA glycosylase (FPG) sites in leucocytes, were measured by medium throughput Comet assay. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was also used to determine the level of oxidative stress.We found higher levels of PM2.5, EC, NO2, SO2 and PAHs in the diesel engine testing workshop and significantly higher urinary 1-OHP concentrations in exposed subjects (p0.001). Compared with controls, the levels of parameters in normal Comet and FPG-Comet assay were all significantly higher in DEE-exposed workers (p0.001), and in a dose-dependent and time-dependent manner. There were no significant differences between DEE-exposed workers and controls in regard to leucocyte FPG sensitive sites and urinary 8-OHdG levels.These findings suggest that DEE exposure mainly induces DNA damage, which might be used as an early biomarker for risk assessment of DEE exposure.

Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to polycyclic aromatic hydrocarbon (PAH)-induced chromosomal damage is of great significance for understanding PAH carcinogenesis. Cytochrome P450, glutathione S-transferase, microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, and N-acetyltransferase are PAH-metabolizing enzymes. In this study, we genotyped for the polymorphisms of these genes and assessed their effects on cytokinesis-block micronucleus (CBMN) frequencies in peripheral blood lymphocytes among 141 coke-oven workers and 66 non-coke-oven worker controls. The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol creatinine, respectively (P0.01). The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 +/- 6.6 per thousand) than in the controls (4.0 +/- 3.6 per thousand; P0.01). Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His113 variant genotype exhibited significantly lower CBMN frequency (8.5 +/- 6.5 per thousand) than did the Tyr113/Tyr113 genotype (11.3 +/- 6.4 per thousand; P0.01); the low mEH activity phenotype exhibited a lower CBMN frequency (8.6 +/- 6.8 per thousand) than did the high mEH activity phenotype (13.2 +/- 6.7 per thousand; P = 0.01); the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 +/- 5.8 per thousand) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 +/- 6.5 per thousand; P0.01); the joint effect of high mEH activity phenotype and GSTM1 null genotype on CBMN frequencies was also found. Gene-environment interactions between occupational PAH exposure and polymorphisms of mEH and/or GSTM1 were also evident. These results indicate that the mEH, GSTP1, and GSTM1 polymorphisms may play a role in sensitivity or genetic susceptibility to the genotoxic effects of PAH exposure in the coke-oven workers.

A wide variety of base damages and single-strand breaks formed by reactive oxygen species during metabolic activation of polycyclic aromatic hydrocarbons (PAHs) have been recognized to be involved in PAH carcinogenesis. In this study, alkaline comet assay was used to detect the DNA damage in peripheral blood lymphocytes among 143 coke-oven workers and 50 non-coke-oven workers, and the effects of genetic polymorphisms of XRCC1 and ERCC2 genes on DNA damage were evaluated. The olive tail moment was significantly higher in coke-oven workers than in non-coke-oven workers (2.6, 95% CI=2.1-3.3 versus 1.0, 95% CI=0.8-1.2, p0.01), and significant correlation between ln-transformed urinary 1-OHP and ln-transformed olive tail moment was found in total population (n=193, Pearson's r=0.393, p0.001) and in coke-oven workers (n=143, Pearson's r=0.224, p=0.007). The olive tail moment was significantly higher in coke-oven workers with GA genotype of G27466A polymorphism of XRCC1 than those with GG genotype (4.6, 95% CI=2.5-8.7 versus 2.4, 95% CI=1.9-2.9, p0.01 with adjustment for covariates). No significant associations between C26304T, G28152A and G36189A polymorphisms of XRCC1 and G23591A and A35931C polymorphisms of ERCC2 and olive tail moment were found in both groups. The study showed that the alkaline comet assay is a suitable biomarker in the detection of DNA damage among coke-oven workers and it suggested that the A allele of G27466A polymorphism of XRCC1 may be associated with decreased DNA repair capacity toward PAH-induced base damage and strand breaks.

Background Although major concerns exist regarding the potential consequences of human exposures to nanoscale carbon black (CB) particles, limited human toxicological data is currently available. The purpose of this study was to evaluate if nanoscale CB particles could be responsible, at least partially, for the altered lung function and inflammation observed in CB workers exposed to nanoscale CB particles. Methods Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and Brunauer-Emmett-Teller were used to characterize CB. Eighty-one CB-exposed male workers and 104 non-exposed male workers were recruited. The pulmonary function test was performed and pro-inflammatory cytokines were evaluated. To further assess the deposition and pulmonary damage induced by CB nanoparticles, male BALB/c mice were exposed to CB for 6 hours per day for 7 or 14 days. The deposition of CB and the pathological changes of the lung tissue in mice were evaluated by paraffin sections and TEM. The cytokines levels in serum and lung tissue of mice were evaluated by ELISA and immunohistochemical staining (IHC). Results SEM and TEM images showed that the CB particles were 30 to 50 nm in size. In the CB workplace, the concentration of CB was 14.90 mg/m3. Among these CB particles, 50.77% were less than 0.523 micrometer, and 99.55% were less than 2.5 micrometer in aerodynamic diameter. The reduction of lung function parameters including FEV1%, FEV/FVC, MMF%, and PEF% in CB workers was observed, and the IL-1β, IL-6, IL-8, MIP-1beta, and TNF- alpha had 2.86-, 6.85-, 1.49-, 3.35-, and 4.87-folds increase in serum of CB workers, respectively. In mice exposed to the aerosol CB, particles were deposited in the lung. The alveolar wall thickened and a large amount of inflammatory cells were observed in lung tissues after CB exposure. IL-6 and IL-8 levels were increased in both serum and lung homogenate. Conclusions The data strongly suggests that nanoscale CB particles could be responsible for the lung function reduction and pro-inflammatory cytokines secretion in CB workers. These results, therefore, provide the first evidence of a link between human exposure to CB and long-term pulmonary effects. Electronic supplementary material The online version of this article (doi:10.1186/s12989-014-0073-1) contains supplementary material, which is available to authorized users.

The International Agency for Research on Cancer has recently reclassified diesel engine exhaust (DEE) as a Group 1 carcinogen. Micronucleus (MN), nucleoplasmic bridge (NPB), and nuclear bud (NBUD) frequencies in peripheral blood lymphocytes (PBLs) are associated with cancer risk. However, the impact of DEE exposure on MN frequency has not been thoroughly elucidated due to mixed exposure and its impact on NPB and NBUD frequencies has never been explored in humans. We recruited 117 diesel engine testing workers with exclusive exposure to DEE and 112 non-DEE-exposed workers, and then we measured urinary levels of 4 mono-hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) using highperformance liquid chromatography-mass spectrometry as well as MN, NPB, and NBUD frequencies in PBLs using cytokinesis-block MN assay. The DEE-exposed workers exhibited significantly higher MN, NPB, and NBUD frequencies than the non-DEE-exposed workers (P < 0.05). Among all study subjects, increasing levels of all 4 urinary OH-PAHs, on both quartile and continuous scales, were associated with increased MN, NPB, and NBUD frequencies (all P < 0.05). When the associations were analyzed separately in DEE-exposed and non-DEE-exposed workers, we found that the association between increasing quartiles of urinary 9-hydroxyphenanthrene (9-OHPh) and MN frequencies persisted in DEE-exposed workers (P ¼ 0.001). The percent of MN frequencies increased, on average, by 23.99% (95% confidential interval, 9.64–39.93) per 1-unit increase in ln-transformed 9-OHPh. Our results clearly show that exposure to DEE can induce increases in MN, NPB, and NBUD frequencies in PBLs and suggest that DEE exposure level is associated with MN frequencies.

Formaldehyde (FA) is a well-known irritant, and it is suggested to increase the risk of immune diseases and cancer. The present study aimed to evaluate the distribution of major lymphocyte subsets and cytokine expression profiles in the peripheral blood of FA-exposed workers. A total of 118 FA-exposed workers and 79 controls were enrolled in the study. High performance liquid chromatography, flow cytometry, and cytometric bead array were used to analyze FA in air sample and formic acid in urine, blood lymphocyte subpopulations, and serum cytokines, respectively. The FA-exposed workers were divided into low and high exposure groups according to their exposure levels. The results showed that both the low and high FA-exposed groups had a significant increase of formic acid in urine when compared to the controls. Both the low and high exposure groups had a significant increase in the percentage of B cells (CD19+) compared to the control group (p

Global hypomethylation, gene-specific methylation, and genome instability are common events in tumorigenesis. To date, few studies have examined the aberrant DNA methylation patterns in coke oven workers, who are highly at risk of lung cancer by occupational exposure to polycyclic aromatic hydrocarbons (PAHs). We recruited 82 PAH-exposed workers and 62 unexposed controls, assessed exposure levels by urinary 1-hydroxypyrene, and measured genetic damages by comet assay, bleomycin sensitivity, and micronucleus assay. The PAHs in coke oven emissions (COE) were estimated based on toxic equivalency factors. We used bisulfite-PCR pyrosequencing to quantitate DNA methylation in long interspersed nuclear element-1 (LINE-1) and O6-methylguanine-DNA methyltransferase (MGMT). Further, the methylation alteration was also investigated in COE-treated human bronchial epithelial (16HBE) cells. We found there are higher levels of PAHs in COE. Among PAH-exposed workers, LINE-1 and MGMT methylation levels (with CpG site specificity) were significantly lowered. LINE-1, MGMT, and its hot CpG site-specific methylation were negatively correlated with urinary 1-hydroxypyrene levels (r = −0.329, p < 0.001; r = −0.164, p = 0.049 and r = −0.176, p = 0.034, respectively). In addition, LINE-1 methylation was inversely associated with comet tail moment and micronucleus frequency, and a significant increase of micronucleus in low MGMT methylation group. In vitro study revealed that treatment of COE in 16HBE cells resulted in higher production of BPDE-DNA adducts, LINE-1 hypomethylation, hypomethylation, and suppression of MGMT expression. These findings suggest hypomethylation of LINE-1 and MGMT promoter could be used as markers for PAHs exposure and merit further investigation.

To investigate the association between the exposure of trichloroethylene (TCE) and chromosomal damage of peripheral lymphocyte of workers.Ninety-one workers exposed to TCE and 59 controls were recruited. Occupational history, age, sex, smoking and alcohol using status of all subjects were collected by questionnaire. Trichloroacetic acid (TCA) in urine was detected as biomarkers of exposure. Micronucleus, nucleoplasmic bridges and nuclear buds in the smear of peripheral blood lymphocytes were counted as indicators of chromosomal damage in terms of cytokinesis-block micronucleus (CBMN) test.The distributions of age, gender, smoking and alcohol consumption were not significantly different between TCE exposed workers and controls. TCA levels in TCE exposed workers were significantly higher than those in controls (57.5 versus 0.9 mg/L, P0.01). No statistically significant difference was observed between the frequencies of micronucleus or nucleoplasmic bridges in TCE exposed workers and controls. Frequencies of nuclear buds in TCE exposed workers were [(1.6 +/- 1.0)%], which were significantly higher (P = 0. 05) than those of controls [(1.2 +/- 0.8) per hundred]. The increase of nuclear buds was most pronounced in the workers with higher TCA (or = 50.0 mg/ L) or longer occupational history (or = 1.8 years). There was a significantly higher frequency of micronucleus [(1.8 +/- 0.9) per hundred] in the workers with a higher TCA level (or = 50.0 mg/L) than the controls [(1.4 +/- 0.7) per hundred, P = 0.05]. No effect of age, gender, smoking and alcohol using on frequencies of micronucleus, nucleoplasmic bridges or nuclear buds was found.TCE exposure could induce some chromosomal damage on occupational exposed workers and nuclear buds might be an effective biomarker for TCE exposure.

To explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and telomere length (TL), so as to investigate the effective biomarkers to evaluate the genetic damage in peripheral blood of workers exposed to PAHs.The exposure group consisted of 145 coke-oven workers (including 30 top-oven workers, 76 side-oven workers and 39 bottom-oven workers), and the non-exposure control group comprised 68 medical staffs. At 6 hours after the weekend duty shift, the samples of urine and 1 ml venous blood were collected from each subject. Airborne benzene-soluble matter (BSM) and particulate-phase B(a)P in the working environment of coke-oven and controls were sampled and analyzed. The concentration of urinary 1-hydroxypyrene (1-OHPyr) was determined. A real-time PCR method was used to determine the relative telomere length (RTL) of genomic DNA in peripheral blood. The relationship between the RTL and external exposure of PAHs, the potential factors which might have influence on TL were analyzed.The medians of air BSM and particulate-phase B(a)P were higher in coke-oven (BSM: 328.6 µg/m(3); B(a)P: 926.9 ng/m(3)) than those in control working environment (BSM:97.8 µg/m(3); B(a)P: 49.1 ng/m(3)). The level of 1-OHPyr among coke-oven workers was significantly higher than that of non-exposed group (12.2 µmol/mol Cr vs 0.7 µmol/mol Cr; t = 26.971, P0.01). RTL in coke-oven workers were significantly shorter than those of controls (1.10 ± 0.75 vs 1.43 ± 1.06; t = 2.263, P = 0.026), and after adjusting for cigarettes per day and urinary 1-OHPyr, the significant difference was still observed (F(adju) = 5.496, P(adju) = 0.020). Stratification analysis found that RTL among the male and non-drinking groups in coke-oven workers were shorter than those the same sex and alcohol using status in controls (1.08 ± 0.73 vs 1.51 ± 1.10, F = 9.212, P = 0.003; 0.96 ± 0.38 vs 1.26 ± 0.46, F = 6.484, P = 0.012). Significant correlation between RTL and age was found (r = -0.284, P = 0.019) in non-exposure group.PAH-exposure has effect on TL of genomic DNA in peripheral blood, which is mainly observed in the male and non-drinking groups between PAH-exposed workers and controls. It indicates that TL of genomic DNA in peripheral blood might be an effective biomarker as PAH-induced genetic damage.

To investigate the influence factors of human peripheral blood B lymphocyte transformation by epstein-barr virus (EBV).EB virus was obtained from B95-8 supernatant and quantitated by quantitative PCR amplification. The concentration of cyclosporine A (CSA) concentration of lymphocytes and different time of adding CSA to culture media were selected to examine the effects on the lymphocyte transformation, and the condition of lymphocyte transformation of worker exposed to trichloroethylene was further confirmed.The titer of two virus samples were 5.45 x 10(6) and 1.06 x 10(6) copies/ml. Peripheral blood mononuclear cells (PBMCs) was transformed by using CSA at different concentration and adding time to culture fluid. The concentration of PBMCs being transformed was 2 x 10(6)/ml for normal people, but 1 x 10(6)/ml for worker exposed to trichloroethylene. Cell transformation was confirmed by the gradual increase of cell size and cellular clusters.The results suggest the key issue is PBMCs being transformed at a concentration of 2 x 10(6)/ml, rather than using CSA at different concentration and adding time to culture fluid. The PBMCs at concentration of 1 x 10(6)/ml for worker exposed to trichloroethylene were transformed, which may be associated with sensitized status of lymphocytes.

DNA and chromosome damages in peripheral blood lymphocytes were evaluated in 151 workers occupationally exposed to formaldehyde (FA) and 112 non-FA exposed controls. The effects of polymorphisms in three glutathione-S-transferase (GSTs) genes on the DNA and chromosome damages were assessed as well. Alkaline comet assay and cytokinesis-block micronucleus (CBMN) assay were used to determine DNA and chromosome damages, respectively. The genotypes of GSTP1 (Ile105Val), GSTT1, and GSTM1 were assayed. The mean 8-h time-weighted average (TWA) concentrations of FA in two plywood factories were 0.83ppm (range: 0.08-6.30ppm). FA-exposed workers had higher olive tail moment (TM) and CBMN frequency compared with controls (Olive TM, 3.54, 95%CI=3.19-3.93 vs. 0.93, 95%CI=0.78-1.10, P0.01; CBMN frequency, 5.51+/-3.37 vs. 2.67+/-1.32, P0.01). Olive TM and the CBMN frequency also had a dose-dependent relation with the personal FA exposure. Significant association between FA exposure history and olive TM and CBMN frequency were also identified. The level of olive TM was slightly higher in FA-exposed workers with GSTM1 null genotype than those with non-null genotype (3.86, 95%CI=3.31-4.50 vs. 3.27, 95%CI=2.83-3.78, P=0.07) with adjustment of covariates. We also found that FA-exposed workers carrying GSTP1 Val allele had a slightly higher CBMN frequency compared with workers carrying only the wild-type allele (6.32+/-3.78 vs. 5.01+/-2.98, P=0.05). Our results suggest that the FA exposure in this occupational population increased DNA and chromosome damages and polymorphisms in GSTs genes may modulate the genotoxic effects of FA exposure.

DNA repair is an essential mechanism for cells to maintain their genomic integrity under endogenous or exogenous assault. Reduced DNA repair capacity (DRC) is associated with increased risk for several environmentally related cancers. The micronucleus in peripheral lymphocytes has been validated as a biomarker of chromosomal damage, increasing cancer risk in human populations. We hypothesized that suboptimal DRC is associated with the increase in chromosomal damage among 94 coke-oven workers and 64 noncoke-oven controls. DRC was evaluated in isolated lymphocytes by comet assay. Chromosomal damage in peripheral lymphocytes was detected by cytokinesis-block micronucleus assay. Four common coding single nucleotide polymorphisms in the XRCC1 gene were genotyped. Coke-oven workers have significantly increased urinary 1-hydroxypyrene (9.0; 6.8-11.7 μg/L versus 1.5, 1.3-1.7 μg/L; P < 0.01) and micronucleus frequency (7.4‰ ± 4.3‰ versus 3.0‰ ± 3.0‰; P < 0.01), and decreased DRC (55.9% ± 16.4% versus 63.6% ± 18.5%; P < 0.01) compared with controls. Significant correlations between DRC and micronucleus frequency were found in coke-oven workers (r = −0.32; P < 0.01; n = 94) and all study subjects (r = −0.32; P < 0.001; n = 158) but not in controls (r = −0.21; P = 0.11; n = 64). Variants of the Arg399Gln polymorphism were associated with a decreased DRC in both coke-oven workers (51.6% ± 16.1% versus 60.6% ± 15.7%; P < 0.01) and controls (59.1% ± 18.5% versus 68.4% ± 17.5%; P = 0.04). The complicated interrelationship of these multiple biomarkers was also identified by path analysis. These findings should facilitate developing a biomarker-based risk assessment model for lung cancer in this occupational population. (Cancer Epidemiol Biomarkers Prev 2009;18(3):987–93)

To seek new effect biomarkers as to evaluating the chromosomal damage in peripheral blood lymphocytes in coke-oven workers who were exposed to polycyclic aromatic hydrocarbons (PAHs).One hundred and fifty-eight coke-oven workers and 69 controls were recruited in this study. Nucleoplasmic bridges and nuclear buds were counted as indicators of chromosomal damage in terms of cytokinesis-block micronucleus (CBMN) test. Occupational history, age, sex, smoking and alcohol using status of all subjects were collected by questionnaire.Frequencies of nucleoplasmic bridge in coke-oven workers were (9.41 +/- 3.73)% per hundred, and the frequencies of nuclear buds were (7.13 +/- 4.01)% per hundred, which were significantly higher (P0.01) than those of controls (1.88 +/- 1.49)% per hundred and (2.20 +/- 1.73)% per hundred respectively. The dose-effect relationships between nucleoplasmic bridges or nuclear buds and PAHs exposure levels were identified. Compared with male coke-oven workers, female workers had less nucleoplasmic bridges or nuclear buds. No effects of age, smoking and alcohol using were found on nucleoplasmic bridges or nuclear buds among coke-oven workers.Nucleoplasmic bridges and nuclear buds might be effect biomarkers in coke-oven workers.

To investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers.Ninty-four coke-oven workers with exposure to a high level of polycyclic aromatic hydrocarbons and 64 non-coke-oven workers (control) were recruited into this study. PBL was challenged by 8 microg/ml BLM, a known carcinogen, to induce certain amount of DNA damage, the difference of olive tail moment (TM) measured by comet assay before and after BLM treatment reflected the sensitivity towards mutagens.The distribution of age, sex, and prevalence of smoking and drinking were not significantly different between these two groups. The geometric mean of urinary 1-hydroxypyrene (1-OHP) was significantly higher in coke-oven workers than in controls (9.0 versus 1.5 microg/L, t = -9.317, P0.01). The coke-oven workers showed significantly higher sensitivity to BLM than controls (17.7 versus 14.9, t = -2.583, P = 0.01). A large inter-group difference in sensitivity to BLM was observed in both controls and coke-oven workers. Stratification analysis revealed the significant association between high 1-OHP level (9.0 microg/L) and increased sensitivity to BLM (F = 4.001, P = 0.05) among coke-oven workers. Smoking subjects showed a significant higher value of sensitivity than nonsmokers in controls but not in coke-oven workers. No significant difference was observed between age, drinking status, coking history or external exposure class and BLM sensitivity.Exposure to coke oven emission could increase the sensitivity to mutagens, which might be a reason of high incidence of lung cancer among coke-oven workers.

To investigate the association of polymorphisms of nucleotide excision repair genes and chromosomal damage in peripheral blood lymphocytes among coke-oven workers.The genotypes of ERCC1 C19007T, ERCC2 C22541A, ERCC2 G23591A, ERCC2 A35931C, ERCC4 T30028C, ERCC5 G3507C and ERCC6 A3368G among 140 coke-oven workers and 66 non-coke-oven controls were determined by PCR-PFLP methods. Chromosomal damage was detected by cytokinesis-block micronucleus (CBMN) assay.Multivariate analysis of covariance revealed that in coke-oven workers, the ERCC1 19007 CC genotype exhibited significantly higher CBMN frequency [(1.05 +/- 0.68)%] than did the CT [(0.81 +/- 0.66)%] (P = 0.01) or TT [(0.66 +/- 0.37)%] (P = 0.05) or CT + TT genotypes [(0.75 +/- 0.63)%] (P = 0.004). For the ERCC6 A3368G polymorphism, AA genotype exhibited significantly higher CBMN frequency [(1.00 +/- 0.69)%] than did the AG [(0.67 +/- 0.42)%] (P = 0.05) or AG + GG genotypes [(0.66 +/- 0.41)%] (P = 0.02). Stratification analysis found the significant association between the two polymorphisms, ERCC1 C19007T and ERCC6 A3368G, and the CBMN frequencies were most pronounced in older workers. In addition, for the polymorphism of ERCC2 G23591A, GA carriers had significantly higher CBMN frequencies [(1.40 +/- 0.63)%] than those GG carriers [(0.98 +/- 0.59)%] (P = 0.01) in older workers.Our results suggested that polymorphisms of ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A were associated with the CBMN frequencies in coke-oven workers.

To investigate the association between polymorphisms of DNA repair gene XRCC1 and DNA damage in peripheral blood lymphocytes among workers exposed to formaldehyde.One hundred and fifty-one workers exposed to formaldehyde from plywood factories and one hundred and twelve workers without occupational exposure to formaldehyde were recruited into this study. DNA damage levels were measured by comet assay. The polymorphisms of XRCC1 gene were analyzed by polymerase chain reaction(PCR) with restriction fragment length polymorphism(RFLP) method. The multiple covariance analysis was used to compare olive trail moment and comet trail length adjusted confounding factors.In formaldehyde exposed workers, after ages, smoking and drinking status and occupational exposure level were adjusted, means of Olive trail moment and comet trail length in the subjects with variant genotype at Arg280 His site (geometric means 4.30 and 13.42 respectively) were higher than subjects with wild type homozygote (geometric means 3.38 and 11.71 respectively), the differences were significant (Olive trail moment: P0.05, comet trail length: P0.01) . No associations between the polymorphisms at other three sites in XRCC1 gene and means of olive trail moment and comet trail length in exposure workers were found.The polymorphisms of XRCC1 gene may modulate the effects of DNA damages induced by formaldehyde in workers.

Carbon black (CB) is a material produced by the combustion of hydrocarbon gases or liquids and widely used in various industrial settings. The International Agency for Research on Cancer has classified CB as possibly carcinogenic to humans. Previous studies suggest that CB might induce lung inflammation and injury and it is well known that inflammation can play an important role in tumor development. However, the relationship between CB exposure and peripheral white blood cell counts is still not clear. To address this issue, we conducted a cross-sectional molecular epidemiology study of 106 CB-exposed male workers responsible for packing CB in a CB manufacturing facility that produced very high purity CB and 112 unexposed male control workers from the same geographic region who were frequency-matched to the exposed workers by age. The average number of years worked in the factory for the exposed workers was 12.5 years. Peripheral blood samples were collected and a complete blood cell count (CBC) and lymphocyte subset analysis were conducted. There was a borderline significant increase in eosinophil count, and a significant decrease in total lymphocyte and NK cell counts, among the exposed vs. control workers. Among non-smokers (35 exposed and 29 controls), CB exposure was associated with a borderline significant increase in total white blood cell and neutrophil counts, a significant increase in eosinophil counts, and a significant decrease in total lymphocyte, CD3+ T cell, CD8+ T cell and NK cell counts. There were no significant differences between exposed and control workers for any white blood cell measure among smokers. Also, there was some evidence of an interaction between carbon black exposure and smoking status for neutrophil, total lymphocyte, CD3+ T cell, and CD8+ T cell counts. Our results suggest that CB exposure may be associated with altered levels of cells that play an important role in the inflammatory process among non-smokers. Also, there was evidence for an interaction between CB exposure and tobacco use. These findings may provide new insights into particulate-associated disease. Citation Format: Yufei Dai, Rong Zhang, Yong Niu, Huawei Duan, Tao Meng, Meng Ye, Meili Shen, Ping Bin, Shanfa Yu, Roel Vermeulen, Nathaniel Rothman, Qing Lan, Yuxin Zheng. Effects of occupational exposure to carbon black on peripheral white blood cell counts. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 839. doi:10.1158/1538-7445.AM2015-839

To investigate the association between genetic polymorphisms of human leukocyte antigen-DQ (HLA-DQ) and susceptibility to trichloroethylene (TCE)-induced severe generalized dermatitis.A case-control study was conducted which included 112 patients with TCE-induced severe generalized dermatitis and 142 healthy controls exposed to TCE in the same workshop. The DNA sequences in exon2 of HLA-DQA1 and HLA-DQB1 were performed by direct sequencing of polymerase chain reaction (PCR) products. The frequencies distribution of allelic genotypes and codon polymorphisms were compared.The frequencies of DQA1*0201 and 060101/0602 in cases [7.6% (17/224) and 16.1% (36/224)] were significantly higher than those of the exposed controls [3.5% (10/284) and 7.0% (20/284)], while frequencies of DQA1*0103 and 050101/0503/0505 in cases [5.8% (13/224) and 8.9% (20/224)] were significantly lower than those of exposed controls [10.9% (31/284) and 17.3% (49/284)]. In terms of codon polymorphisms, there were 5 codons of DQA1 (25, 41, 52, 54 and 69) showing significant differences between cases and controls. There were no significant differences in the frequencies of allelic genotypes of HLA-DQB1 between cases and exposed controls.The genetic polymorphisms of HLA-DQA1 might be one of the factors influencing the individual susceptibility to TCE-induced severe generalized dermatitis.

To investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers.The study included 141 coke-oven workers who exposed to a high level of polycyclic aromahaplotpetic hydrocarbon and 66 non-exposed controls. Urinary 1-hydroxypyrene and chromosome damage in peripheral lymphocyte were measured. Four -tagging single nucleotide polymorphisms in XRCC1 gene, including C26304T, G27466A, G28152A and G36189A, were detected and the XRCC1 haplotypes were estimated by using an extension of Clark algorithm. The associations between haplotype pairs and micronuclei data were assessed by analysis of covariance in the exposed and non-exposed groups.The geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol Cr respectively (P0.01). The cytokinesis-block micronucleus cytokinesis-block micronucleus frequencies (number of micronucleus per 1 000 binucleated lymphocytes) was significantly higher in coke-oven workers (0.95 +/- 0.66)% than in the controls (0.40 +/- 0.36)%, P0.01. The haplotype CGGG was associated with the decreased frequencies of total micronucleus, and the haplotypes TGGG (P = 0.01) and CGAG (P0.05) were associated with the increased frequencies of total micronucleus in the multivariate analysis with adjustment for covariates among coke-oven workers.The genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.

To investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers.One hundred and forty-four coke-oven workers and 50 controls were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of polycyclic aromatic hydrocarbons exposure. DNA damage was detected by alkaline comet assay, and the value of 1.74 was used as the cut-off value to determine whether the individual's DNA damage was positive. The genotypes of CYP1A1, CYP2E1, GSTP1, NQO1, mEH and XRCC1 were determined by PCR-based methods. With adjustment for urinary 1-OHP, age, sex, multiple analysis of covariance was used to study the association between genotypes and the ln-transformed olive TM and multiple logistic regression was used to calculate the adjusted OR and the 95% CI for the risk of DNA damage.In 144 coke-oven workers, with adjustment for urinary 1-OHP, coking history and sex, the olive TM was significantly higher with XRCC1 280His allele than those with Arg allele (5.6 vs. 2.8, P0.01). The subjects with XRCC1 280His allele also have significantly higher risk for DNA damage than subjects with Arg allele (adjusted OR = 2.66, 95% CI = 1.00-7.14, P = 0.05) and the subjects with GSTP1 104Val allele have higher risk for DNA damage than subjects with Ile allele (adjusted OR = 1.90, 95% CI = 0.94-3.85, P = 0.07).XRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.

To investigate the associations of polymorphisms of metabolic enzyme genes with urinary 1-hydroxypyrene levels in coke oven workers.One hundred and forty-eight workers from a coke oven plant and 69 controls without occupational PAHs exposure were selected in this study. Urinary 1-hydroxypyrene was detected by high performance liquid chromatography with florescence detector. The genotypes at I462V site in exon 7 of CYP1A1 gene, GSTM1, GSTT1, I105V site in GSTP1gene, Pst1 and Dra1 sites in CYP2E1 gene, P187S site in NQO1 gene, Kpn1, BamH1 and Taq1 sites in NAT2 gene, and H113Y, R139H sites in mEH gene were determined by PCR-based methods. Personal information including occupational exposure history, age, sex, smoking and drinking status was collected by the questionnaire.The level of urinary 1-hydroxypyrene in coke oven workers [(5.61 +/- 1.04) mol/mol Cr] was higher than that in control [(0.74 +/- 0.32) micro mol/mol Cr]. After adjusting external occupational exposure category and smoking, coke oven workers with variant homozygotes at H113Y site of mEH gene had significantly higher urinary 1-hydroxypyrene concentrations than those with heterozygotes, and wild homozygotes (6.41 +/- 1.09 vs. 6.24 +/- 1.08, and 4.62 +/- 0.95 micro mol/mol Cr, P0.05), and gene-gene interaction was found between CYP1A1 and mEH.Genetic polymorphism of mEH gene could be a susceptible biomarker in coke oven workers which was involved in the individual susceptibility on metabolism of PAHs.

To investigate the relationship between lymphocyte DNA damage and polycyclic aromatic hydrocarbons (PAHs) exposure in coke oven workers.Two hundred and thirty-five coke oven workers and 30 controls were selected in this study. Alkaline single-cell gel electrophoresis was used to evaluate the lymphocyte DNA damage, HPLC was employed to measure 1-hydroxypyrene levels in spot urine samples which were obtained at the end of a workweek (4 days of 8 hours/day) and personal information including occupational exposure, age, sex, smoking and drinking status was collected by the questionnaire.The lymphocyte DNA damage level expressed as olive moment in coke oven workers was significantly higher than that of controls [2.47 (0.22 approximately 46.68) vs 0.94 (0.42 approximately 4.21), P0.01], and correlation between urinary 1-hydroxypyrene concentrations and olive moment was found (Spearman Partial correlation coefficient = 0.22, P0.01) in coke oven workers. The 1.9 of olive moment value was used as the limit to determine whether the subject DNA damage was positive. The coke oven workers had significantly higher risk in DNA damage (adjusted OR = 5.38, 95% CI = 2.07 approximately 14.08) than did controls, and dose-response relationships were also found between external exposure (exposure category) or internal doses (urinary 1-hydroxypyrene) and DNA damage.There are dose-effect and dose-response relationships between PAHs exposure and lymphocyte DNA damage in coke oven workers.

To investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.One hundred and fourty-nine coke oven workers and 24 referents without occupational polycyclic aromatic hydrocarbons (PAH) exposure were recruited in this study. Urinary 1-hydroxypyrene levels were measured as the internal dose of PAH exposure. The 6 per 1 000 of micronucleus value was used as the cut-off value to determine whether the individual's chromosomal damage was positive. The genotypes of CYP1A1, GSTM1, GSTT1, GSTP1, CYP2E1, NQO1, NAT2 and mEH genes were determined by PCR-based methods. Multiple logistic regression was used to calculate the adjusted ORs and the 95% CI for the risk of chromosomal damage and to analyze the gene-gene interaction.In 173 subjects, after adjusting the occupational exposure, age, sex, smoking and drinking status, the subjects with GSTM1 null genotype have significantly higher risk for chromosomal damage than subjects with GSTM1 positive genotype (adjusted OR = 2.01, 95% CI = 1.03 -3.91). Compared with the wild homozygotes at P187S site of NQO1 gene, the variant homozygotes have significantly higher risk for chromosomal damage (adjusted OR = 3.18, 95% CI = 1.18 - 8.62). The subjects with variant allele at H113Y site of mEH gene have significantly lower risk for chromosomal damage (adjusted OR = 0.40, 95% CI = 0.19 - 0.88). No significant associations were found for other gene polymorphisms and chromosomal damage risk. In addition, the gene-gene interactions were also found among GSTM1, NQO1 gene P187S and mEH gene H113Y polymorphisms for the risk of chromosomal damage risk.Significant associations between genetic polymorphisms in GSTM1, NQO1 and mEH gene and risk for chromosomal damage were found among occupational PAH-exposed workers, which related to the mechanism of PAH carcinogenesis.

To investigate DNA and chromosome damage in peripheral blood lymphocyte of coke oven workers exposed to polycyclic aromatic hydrocarbons (PAHs).One hundred and thirty-seven coke oven workers and 50 controls without occupational PAHs exposure were investigated. Comet assay and cytokinesis-block micronucleus (CBMN) detection were used to evaluate DNA and chromosomal damage levels in peripheral blood lymphocyte. Urinary 1-hydroxypyrene level was used to assess the personal internal PAHs exposure dose. Personal information including occupational history, age, sex, smoking and drinking status was collected by questionnaire.Urinary 1-hydroxypyrene level in coke oven workers [(5.76 +/- 1.04) micro mol/mol Cr] was significantly higher than that in controls [(0.70 +/- 0.32) micro mol/mol Cr]. The rate of CBMN and comet tail moment of lymphocyte in coke oven workers [8.0 per thousand (0.0 per thousand - 30.0 per thousand ) and 2.09 (0.31 - 75.41), respectively] were higher than those in controls [3.5 per thousand (0.0 per thousand - 13.0 per thousand ) and 1.05 (0.11 - 6.63), P0.05]. In controls, the comet moment in smokers was significantly higher than that in non-smokers [1.44 (0.23 - 6.63) vs 0.81 (0.11 - 3.47), P0.05]. According to the length of work, 137 coke oven workers were classified into 3 groups i.e. 0.5 yrs , 16.0 yrs and 22.0 yrs group, and the comet moments were 1.34 (0.31 - 37.84), 2.32 (0.49 - 52.97) and 3.20 (0.45 - 75.41) respectively after adjusting the age, sex, smoking, drinking and level of urinary 1-hydroxy-pyrene. There was a rising tendency along with the increase in length of work.Under present PAHs exposure levels, both comet assay and Cytokinesis-block micronucleus test could detect PAHs-induced genotoxicity in coke oven workers, and comet assay is more suitable to assess the cumulative damage effect on DNA.

To investigate the relationship between the urinary 1-hydroxypyrene level and cytokinesis-block micronucleus and the olive moment of comet assay in peripheral blood lymphocyte in coke oven workers.One hundred and thirty-three workers from a coke plant and 28 referents without occupational PAH exposure were recruited in this study. Urinary level of 1-hydroxypyrene was measured by alkaline hydrolysis combined with high performance liquid chromatography as an internal exposure dose, and the DNA and chromosomal damage of peripheral blood lymphocyte were evaluated with comet assay and cytokinesis-block micronucleus method. Personal information including occupational history, age, sex, smoking and alcohol drinking, was collected by questionnaire.There existed a good correlationship between the urinary level of 1-hydroxypyrene and frequency of micronuclei per 1 000 binucleated cells or the olive moment of comet assay in the study subjects, after adjusting for sex, age, smoking and alcohol drinking (r0.25, P0.01). One hundred and sixty-one subjects were divided into three groups by their urine 1-hydroxypyrene level (expressed as 0.30 - 2.44, 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr), and the geometric means of their urinary levels of 1-hydroxypyrene were 1.14, 4.32 and 12.49 micro mol/mol Cr, respectively. After adjusting for age, sex, smoking and alcohol drinking by multiple nonparametric analysis of covariance, the median of olive moment of comet assay in the group of 7.10 - 33.10 micro mol/mol Cr was 3.67, significantly higher than that in the groups of 0.30 - 2.44 and 2.45 - 7.09; and the micronuclei frequencies in the groups of 2.45 - 7.09 and 7.10 - 33.10 micro mol/mol Cr were 8.00 per thousand and 7.50 per thousand, respectively, significantly higher than that in the group of 0.30 - 2.44 micro mol/mol Cr (6.00 per thousand ).The comet assay of peripheral blood lymphocyte was more suitable to detect the PAHs-induced early genotoxicity, than the cytokinesis-block micronucleus.