Cytogenetic analysis of coke oven workers in Eastern Slovakia.

OBJECTIVE: Our study aimed to evaluate the extent of polycyclic aromatic hydrocarbon (PAH) exposure in coke oven workers from Eastern Slovakia by cytogenetic analysis of human peripheral lymphocytes. METHODS: A total of 81 peripheral blood samples were collected from PAH-exposed workers (mean age 45.84 ± 9.73 years) and 30 samples constituted the control group (41.93 ± 15.39 years). The samples were processed using routine cytological analysis. Conventional cytogenetic analysis of human peripheral lymphocytes has been used to evaluate the effects of PAHs. RESULTS: Comparison of the aberrant cells in the total exposed with the controls showed a significant difference (p < 0.05). A high level of significance (p < 0.001) was observed when comparing the gaps between the exposed group and the control group. There was a significant difference (p < 0.01) in aberrant cells and chromatid breaks (p < 0.05) in the GR1 working subgroup compared with the control group. The results of the correlation analysis did not show a significant relationship between the length of occupational exposure and the frequency of aberrant cells (r = 0.071, p = 0.529). Similarly, no association was observed between smoking among coke plant workers and the frequency of aberrant cells (r = 0.117, p = 0.538). CONCLUSION: Cytogenetic analysis showed an increased frequency of chromosomal aberrations in coke oven workers in Eastern Slovakia.

Association between urinary polycyclic aromatic hydrocarbons metabolites and high-normal blood pressure in coke oven workers / 中国职业医学

@#Objective （ ） To investigate the association between urinary polycyclic aromatic hydrocarbons PAHs metabolites - Methods and high normal blood pressure in coke oven workers. A total of 433 coke oven workers were selected as the study - subjects using convenient sampling method. They were divided into normal blood pressure group and high normal blood pressure group according to their blood pressure level. The levels of ten kinds of urinary hydroxylated PAHs metabolites were measured by - Results - high performance liquid chromatography mass spectrometry. Among the subjects,57.5% had high normal blood - ， - ， - pressure. The levels of 1 hydroxynathalene 2 hydroxyphenanthrene 1 hydroxyphenanthrene and the metabolite of total PAHs - （ P ） in the high normal blood pressure group were higher than those in the normal blood pressure group all <0.05 . The results of - ， - ， - ， the multivariate logistic regression analysis showed that urinary 1 hydroxynathalene 2 hydroxyfluorene 3 hydroxychrysene - （ P ）， and metabolite of total PAHs were all risk factors for high normal blood pressure in coke oven workers all <0.05 after ， ， ， ， ， adjusting for confounding factors such as gender length of service body mass index smoking index alcohol consumption tea ， ， ， Conclusion consumption night shift exercise frequency and other PAHs metabolites. Exposure to PAHs in coke oven plants may increase the risk of elevated blood pressure within the normal range among coke oven workers.

Global H3K79 di-methylation mediates DNA damage response to PAH exposure in Chinese coke oven workers.

Polycyclic aromatic hydrocarbons (PAHs) are the main contaminants of coke oven emissions which can induce serious genetic damage in coke oven workers. Epigenetic alternations play essential roles in the regulation of DNA damage effect of PAHs. Previous studies indicate that H3K79 di-methylation (H3K79me2) is integral in DNA damage repair. However, the potential role of H3K79me2 in DNA damage response (DDR) following PAHs exposure is still unclear. In this study, we recruited 256 male coke oven workers and control workers, and examined H3K79me2 and DNA damage in their peripheral blood lymphocytes (PBLCs). The results showed that global H3K79me2 of coke oven workers was 29.3% less than that of the controls (P < 0.001). The H3K79me2 was negatively correlated with the concentration of urinary 1-hydroxypyrene (1-OHP) (ß = -0.235, P < 0.001) and level of genetic damage evaluated by comet assay (ßTail DNA % = -0.313, P < 0.001; ßOTM = -0.251, P = 0.008). Consistently, we found that benzo(a)pyrene (BaP) inhibited H3K79me2 in immortalized human bronchial epithelial (HBE) cells in a time-dependent manner. In order to explore the function of H3K79me2 in PAHs DDR, we established histone 3.1/3.3 K79A mutant cells (H3K79 A) to suppress H3K79me2. H3K79 A cells showed more serious DNA damage and decreased cell viability than control cells after BaP treatment. In addition, we also found that the expression of DOT1L, the only methyltransferase in H3K79, was repressed by BaP dose-dependently. DOT1L knockdown resulted in decreased H3K79me2 level and aggravated DNA damage after BaP exposure. This suggests that BaP induces H3K79me2 repression via inhibiting DOT1L expression. In conclusion, these findings indicate that PAH exposure decreases the level of global H3K79me2, which is integral for DNA damage response regulation of PAHs.

Urinary Mercapturic Acids to Assess Exposure to Benzene and Other Volatile Organic Compounds in Coke Oven Workers.

Coke production was classified as carcinogenic to humans by the International Agency for Research on Cancer. Besides polycyclic aromatic hydrocarbons, coke oven workers may be exposed to benzene and other volatile organic compounds (VOCs). The aim of this study was to assess the exposure to several VOCs in 49 coke oven workers and 49 individuals living in the same area by determining urinary mercapturic acids. Active tobacco smoking was an exclusion criterion for both groups. Mercapturic acids were investigated by a validated isotopic dilution LC-MS/MS method. Linear models were built to correct for different confounding variables. Urinary levels of N-acetyl-S-phenyl-L-cysteine (SPMA) (metabolite of benzene), N-acetyl-S-(2-hydroxy-1/2-phenylethyl)-L-cysteine (PHEMA) (metabolite of styrene), N-acetyl-S-(2-cyanoethyl)-L-cysteine (CEMA) (metabolite of acrylonitrile), N-acetyl-S-[1-(hydroxymethyl)-2-propen-1-yl)-L-cysteine and N-acetyl-S-(2-hydroxy-3-buten-1-yl)-L-cysteine (MHBMA) (metabolites of 1,3-butadiene) were 2-10 fold higher in workers than in controls (p < 0.05). For SPMA, in particular, median levels were 0.02 and 0.31 µg/g creatinine in workers and controls, respectively. Among workers, coke makers were more exposed to PHEMA and SPMA than foremen and engine operators. The comparison with biological limit values shows that the exposure of workers was within 20% of the limit values for all biomarkers, moreover three subjects exceeded the restrictive occupational limit value recently proposed by the European Chemicals Agency (ECHA) for SPMA.

Benchmark dose assessment for coke oven emissions-induced telomere length effects in occupationally exposed workers in China.

Telomeres are DNA-protein structures that protect chromosome ends from degradation and fusion, which are shortened by oxidative stress, for example air pollution including benzene, toluene, Coke Oven Emissions (COEs), and so on. As a biomarker of health and disease, telomere length is associated with cardiovascular, diabetes and cancers. The aim of this study was to estimate the effects of COEs exposure on telomere length and the benchmark dose (BMD) of COEs. A total of 542 coke oven workers and 235 healthy controls without exposure to toxicants were recruited. Quantitative PCR was used to determine the telomere length in human peripheral blood leukocytes DNA. Propensity scoring was used to match coke oven workers to healthy controls. Linear regression models and trend tests were used to the relationship between COEs exposure and telomere length. Telomere length in COEs exposed group 0.764 (0.536, 1.092) was significantly shorter than that in the control group 1.064(0.762, 1.438), (P < 0.001). There were significantly dose-response relationships between COEs exposure and telomere damage with telomere length as a biomarker. A BMDL value lower than the present occupational exposure limits (OELs) of COEs exposure was evaluated using the BMD approach in coke oven workers. Our results suggested that shorter telomere length is related to occupational exposure to COEs and the level of COEs exposure lower than the current national OELs in China and many other countries could induce telomere damage.

[Effects of smoking on concentration of urinary 8-hydroxydeoxyguanosine in coke oven workers].

Objective: To explore the influence of smoking and polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxydeoxyguanosine (8-OHdG) in coke oven workers and investigate their dose-dependent relationships. Methods: A total of 436 workers exposed to coke oven emissions (COEs) and 132 controls were recruited in this study. Questionnaires were completed in a personal interview. Then their urine samples were also collected and the concentrations of urinary four OH-PAHs and 8-OHdG were determined by high performance liquid chromatography (HPLC) which was used to evaluate the levels of occupational PAHs internal exposure among workers and the DNA damage. Results: The differences of concentrations of urinary 2-NAP (2-hydroxynathalene) , 2-FLU (2-hydroxyfluorene) , 9-PHE (9-hydroxyphenanthrene) , 1-OHP (1-hydroxypyrene) between exposure group and control group were statistically significant (P<0.05) . In exposure group and control group, the level of 8-OHdG in heavy smoking workers were significantly higher than that in other groups (P<0.05) . Multivariate logistic regression analysis revealed high levels of urinary 8-OHdG were associated with a significantly increased risk of having higher urinary1-hydroxypyrene levels[OR=1.43 (95%CI: 1.06-1.94) , P<0.01] and heavy smoking [OR=1.44 (95%CI: 1.08-1.91) , P<0.01], respectively. Trend test showed that linear dose response relationship between smoking, 1-OHP in urine and higher concentrations of 8-OHdG (P<0.05) . Smoking could significant modify the effects of urinary 1-hydroxypyrene, while co-exposure to both heavy smoking and high urinary 1-hydroxypyrene levels[OR=5.64 (95%CI: 2.15-14.80) , P<0.05]. Conclusion: Urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure, coke oven workers with heavy smoking present more serious DNA oxditive damage.

Association of polycyclic aromatic hydrocarbons metabolites and risk of diabetes in coke oven workers.

Elevated polycyclic aromatic hydrocarbons (PAHs) metabolites have recently been linked to increased risk of diabetes in the general population, but little is known about the risk of diabetes due to high pollution levels of PAHs exposure. We aimed to examine whether occupational exposure to PAHs would be one of the important risk factors for diabetes in the coke oven workers. A total of 1472 coke oven workers with complete data were qualified for the present study. We measured 12 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) by gas chromatography-mass spectrometry (GC-MS). Multiple logistic regression was used to evaluate the associations between urinary OH-PAHs and risk of diabetes, with adjustment for the potential confounders. We found that elevated urinary 4-hydroxyphenanthrene (4-OHPh) was significantly associated, in a dose-dependent manner, with increased risk of diabetes (Ptrend = 0.003). Compared with individuals with 4-OHPh in the lowest quartile, the adjusted odds ratio (OR) of diabetes among those in the highest quartile was 2.80 (95% CI = 1.37-5.71). In stratified analysis, the association was more prominent in those who were smokers, overweight (BMI ≥24 kg/m2), with longer working years (≥20 years) and worked at coke oven settings. In addition, high levels of 4-OHPh combined with longer working years or overweight had a joint effect on the risk of diabetes. Our data suggested that elevated 4-OHPh was dose-responsive associated with increased risk of diabetes in the coke oven workers. The risk assessment of diabetes related to occupational PAHs exposure should take working years and BMI into consideration.

Effects of smoking on concentration of urinary 8-hydroxydeoxyguanosine in coke oven workers / 中华劳动卫生职业病杂志

Objective@#To explore the influence of smoking and polycyclic aromatic hydrocarbons (PAHs) on urinary 8-hydroxydeoxyguanosine (8-OHdG) in coke oven workers and investigate their dose-dependent relationships.@*Methods@#A total of 436 workers exposed to coke oven emissions (COEs) and 132 controls were recruited in this study. Questionnaires were completed in a personal interview. Then their urine samples were also collected and the concentrations of urinary four OH-PAHs and 8-OHdG were determined by high performance liquid chromatography (HPLC) which was used to evaluate the levels of occupational PAHs internal exposure among workers and the DNA damage.@*Results@#The differences of concentrations of urinary 2-NAP (2-hydroxynathalene) , 2-FLU (2-hydroxyfluorene) , 9-PHE (9-hydroxyphenanthrene) , 1-OHP (1-hydroxypyrene) between exposure group and control group were statistically significant (P<0.05) . In exposure group and control group, the level of 8-OHdG in heavy smoking workers were significantly higher than that in other groups (P<0.05) . Multivariate logistic regression analysis revealed high levels of urinary 8-OHdG were associated with a significantly increased risk of having higher urinary1-hydroxypyrene levels[OR=1.43 (95%CI: 1.06-1.94) , P<0.01] and heavy smoking [OR=1.44 (95%CI: 1.08-1.91) , P<0.01], respectively. Trend test showed that linear dose response relationship between smoking, 1-OHP in urine and higher concentrations of 8-OHdG (P<0.05) . Smoking could significant modify the effects of urinary 1-hydroxypyrene, while co-exposure to both heavy smoking and high urinary 1-hydroxypyrene levels[OR=5.64 (95%CI: 2.15-14.80) , P<0.05].@*Conclusion@#Urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure, coke oven workers with heavy smoking present more serious DNA oxditive damage.

Association of urinary metals levels with type 2 diabetes risk in coke oven workers.

BACKGROUND: Studies indicated that occupationally exposed to metals could result in oxidative damage and inflammation and increase cardiovascular diseases risk. However, epidemiological studies about the associations of metals exposure with diabetes risk among coke oven workers were limited. OBJECTIVES: This study aims to investigate the potential associations of 23 metals levels with the risk of diabetes among coke oven workers. METHODS: The analysis was conducted in a cross-sectional study including 1493 participants. Urinary metals and urinary polycyclic aromatic hydrocarbons (PAHs) metabolites levels were determined by inductively coupled plasma mass spectrometer and gas chromatograph-mass spectrometer respectively. Multivariate logistic regression was used to investigate the associations of urinary metal levels with diabetes risk with adjustment for potential confounding factors including gender, age, BMI, education, smoking, drinking, physical activity, hypertension, hyperlipidemia and urinary PAHs metabolites levels. RESULTS: Compared with the normoglycemia group, the levels of urinary copper, zinc, arsenic, selenium, molybdenum, and cadmium were significantly higher in the diabetes group (all p < 0.05). Participants with the highest tertile of urinary copper and zinc had 2.12 (95%CI: 1.12-4.01) and 5.43 (95%CI: 2.61-11.30) fold risk of diabetes. Similar results were found for hyperglycemia risk. Besides, participants with the highest tertile of manganese, barium, and lead had 1.65(1.22-2.23), 1.60(1.19-2.16) and 1.45(1.05-1.99) fold risk of hyperglycemia when compared with the lowest tertlie. CONCLUSION: The results indicated that the urinary copper and zinc levels were positively associated with the risk of diabetes and hyperglycemia among coke oven workers. Urinary manganese, barium and lead levels were also associated with increased risk of hyperglycemia independently of other traditional risk factors. These findings need further validation in prospective study with larger sample size.

Urinary carcinogenic 4-6 ring polycyclic aromatic hydrocarbons in coke oven workers and in subjects belonging to the general population: role of occupational and environmental exposure.

AIM: A new solid phase microextraction-gas chromatography-mass spectrometry method (SPME-GC-MS) to detect urinary unmetabolized 3-, 6-ring polycyclic aromatic hydrocarbons (PAHs) was applied to coke oven workers and general population subjects with the aim to assess exposure to carcinogenic PAHs, to evaluate the role of occupational and environmental variables on PAHs levels, and to compare present results with those previously obtained with a less sensitive method. METHODS: A total of 104 coke oven workers (CW) from Poland [recruited in 2000 (CW-2000; n=55) and 2006 (CW-2006; n=49)], and 45 control subjects from the same area, provided urine spot samples for measurement of 10 PAHs (from phenanthrene to benzo[g,h,i]perylene). The comparison between the two methods was performed only on CW-2000 subjects. Information regarding personal characteristics and job variables was collected by a questionnaire. RESULTS: The new method enables the quantification of 5-, 6-ring PAHs; precision and accuracy were in the 7.3-20.8% and 89.4-110% range, respectively; in CW-2000 samples results obtained with the new and the old method were highly correlated (Lin's concordance correlation coefficients: from 0.790 to 0.965); the mean difference between measured PAHS increased with the molecular weight of the analytes (from +5 to +27%). Urinary PAHs were above or equal to the quantification limit, depending on the compound, in 67-100% (min-max), 26-100% and 6-100% of samples from CW-2000, CW-2006 and controls, respectively. Chrysene and benz[a]anthracene were the most abundant carcinogenic PAHs with median levels of 43.4, 13.4, and 2.3 ng/L and 45.9, 14.9, and 0.7 ng/L in CW-2000, CW-2006, and controls, respectively, while benzo[a]pyrene levels were 6.5, 0.7 and <0.5 ng/L. The multiple linear regression model showed that the determinants of exposure were the use of wood and/or coke for house heating for controls, and job title or the plant for CW-2006. CONCLUSIONS: Urinary benzo[a]pyrene and other carcinogenic PAHs were, for the first time, quantified in urine samples from both occupationally and environmentally exposed subjects. These results show that urinary PAHs can discriminate exposure at different levels. Moreover, the simultaneous determination of several PAHs allows for the development of excretion profiles to assess exposure to specific compounds.

Using lymphocyte and plasma Hsp70 as biomarkers for assessing coke oven exposure among steel workers.

BACKGROUND: Hsp70, an early-response protein induced when organisms are confronted with simple or complicated environmental stresses, can act as either a cellular protector or a danger signal. OBJECTIVES: The goal of this study was to evaluate levels of lymphocyte and/or plasma Hsp70 as biomarkers for assessing exposure response to complex coke oven emissions (COEs). METHODS: We recruited 101 coke oven workers and determined levels of polycyclic aromatic hydrocarbon (PAH) exposure, urinary 1-hydroxypyrene (1-OHP), genotoxic damage by comet assay and micronuclei test, and other markers of damage, including plasma malondialdehyde (MDA) and lactate dehydrogenase (LDH). These were compared to levels of lymphocyte (intra-cellular) and plasma (extracellular) Hsp70 using Western blots and enzyme-linked immunosorbent assays (ELISA), respectively. RESULTS: We observed a COEs-related dose-dependent increase in levels of DNA damage, micronuclei rate, MDA concentration, and LDH activity. Lymphocyte Hsp70 levels increased in the intermediate-exposure group (1.39 +/- 0.88) but decreased in the high-exposure group (1.10 +/- 0.55), compared with the low-exposure group. In contrast, plasma Hsp70 levels progressively increased as the dose of exposure increased. Negative correlations were seen between lymphocyte Hsp70 levels and olive tail moment and LDH activity in the intermediate- and high-exposure groups. However, we observed positive correlations between plasma Hsp70 levels and LDH activity in the low and intermediate groups. CONCLUSIONS: In workers exposed to COEs, high lymphocyte Hsp70 levels may provide protection and high plasma Hsp70 levels may serve as a danger marker. Larger validation studies are needed to establish the utility of Hsp70 as a response marker.

Cytochrome P450 (CYP) and glutathione S-transferases (GST) polymorphisms (CYP1A1, CYP1B1, GSTM1, GSTP1 and GSTT1) and urinary levels of 1-hydroxypyrene in Turkish coke oven workers

Genetic polymorphisms of xenobiotic metabolizing enzymes have been associated with cancer risk. We evaluated the influences of genetic polymorphisms of polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes on urinary 1-hydroxypyrene (1-OHP) excretion in Turkish coke oven workers. Urinary 1-OHP was analyzed by HPLC after enzymatic hydrolysis. Lymphocyte DNA was used for PCR-based genotyping of cytochrome P450 (CYP) polymorphisms (CYP1A1 and CYP1B1) and glutathione S-transferases (GST) polymorphisms (GSTM1, GSTT1 and GSTP1). The mean urinary 1-OHP levels of coke oven workers were significantly higher than that of controls. No significant difference was detected in the mean urinary 1-OHP levels of smokers and non-smokers either for coke oven workers or controls. Genetic polymorphisms of the CYPs and GSTs studied had no significant influence on 1-OHP excretion in coke oven workers, but in the control group the urinary 1-OHP levels of individuals carrying the GSTT1- genotype were significantly higher than those of individuals carrying GSTT1+ genotype. The duration of occupational exposure and metabolic genotype for GSTT1 were the significant predictors of urinary 1-OHP levels. The control individuals carrying combined GSTM1-/GSTT1- genotypes also had significantly higher levels of urinary 1-OHP than those of individuals carrying GSTM1+/GSTTI+, GSTM1-/GSTT1+, and GSTM1+/GSTT1- genotypes. These results indicate that urinary 1-OHP is a sensitive indicator of recent human exposure to PAHs and that genetic polymorphism of GSTT1 may also to some extent reflect the interindividual variation in susceptibility to PAHs only at low PAH exposure.