OBJECTIVETo investigate the association between the polymorphisms of metabolic genes and telomere length of genomic DNA in peripheral blood of workers exposed to polycyclic aromatic hydrocarbons (PAHs).

METHODSOne hundred and forty five coke-oven workers exposed to PAHs and sixty eight non-exposed medical staffs were recruited in this study. Urinary 1-hydroxypyrene (1-OHP) served as the internal exposure dose of PAHs for all subjects. Relative telomere length (RTL) of genomic DNA in peripheral blood was used as telomere length and measured by real-time PCR. Polymorphisms of metabolic genes were detected by PCR-based methods.

RESULTSCompared with control group, the exposure group shown a decreased RTL (1.10 +/- 0.75 vs 1.43 +/- 1.06, P < 0.05). In the coke-oven workers, after adjusting the sex, age, cigarettes per day and urinary 1-OHP, RTL (1.25 +/- 0.93) of workers with CT genotype at the CYP1A1 3801 T > C was significantly longer than that (0.93 +/- 0.51) of workers with TT genotype (P < 0.05). RTL (0.90 +/- 0.58) of individuals with the Tyr/His genotype at mEH Tyr113His was significantly shorter than that (1.24 +/- 0.90) of individuals with the Tyr/Tyr genotype (P < 0.05). RTL (1.02 +/- 0.64) of individuals with the CT genotype at AHR rs10250822 was significantly shorter than that (1.36 +/- 1.14) of individuals with the CC genotype (P < 0.05). RTL (0.93 +/- 0.54) of individuals with the AT genotype at AHR rs10247158 was significantly shorter than that (1.19 +/- 0.84) of individuals with the AA genotype (P < 0.05).

CONCLUSIONThe results of present study suggested that PAHs exposure could induce the shorted RTL, CYP1A1, mEH, AHR polymorphisms might influence the change of telomere length of genomic DNA in peripheral blood of workers exposed to PAHs.

Adult ; Case-Control Studies ; Cytochrome P-450 CYP1A1 ; genetics ; DNA ; genetics ; DNA Damage ; Female ; Genotype ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; toxicity ; Polymorphism, Single Nucleotide ; Telomere ; genetics ; Young Adult

OBJECTIVETo 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.

METHODSThe 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.

RESULTSThe 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, P < 0.01). 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.

CONCLUSIONPAH-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.

Adult ; Benzene ; Case-Control Studies ; Coke ; DNA Damage ; Female ; Humans ; Male ; Occupational Exposure ; adverse effects ; analysis ; Polycyclic Aromatic Hydrocarbons ; adverse effects ; analysis ; Pyrenes ; analysis ; Telomere ; drug effects ; genetics

OBJECTIVETo 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).

METHODSOne 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.

RESULTSFrequencies 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 (P < 0.01) 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.

CONCLUSIONNucleoplasmic bridges and nuclear buds might be effect biomarkers in coke-oven workers.

Adult ; Alcohol Drinking ; Cell Nucleus ; Coke ; DNA Damage ; Female ; Humans ; Lymphocytes ; Male ; Micronucleus Tests ; Occupational Exposure ; analysis ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Smoking

OBJECTIVETo investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers.

METHODSNinty-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.

RESULTSThe 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, P < 0.01). 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.

CONCLUSIONExposure 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.

Adult ; Benzo(a)pyrene ; toxicity ; Bleomycin ; toxicity ; Coke ; Comet Assay ; DNA Damage ; DNA Repair ; Female ; Humans ; Lymphocytes ; drug effects ; Male ; Middle Aged ; Mutagens ; toxicity ; Occupational Exposure

OBJECTIVETo investigate the association of polymorphisms of nucleotide excision repair genes and chromosomal damage in peripheral blood lymphocytes among coke-oven workers.

METHODSThe 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.

RESULTSMultivariate 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.

CONCLUSIONSOur results suggested that polymorphisms of ERCC1 C19007T, ERCC6 A3368G and ERCC2 G23591A were associated with the CBMN frequencies in coke-oven workers.

Adult ; Alcohol Drinking ; Coke ; Comet Assay ; DNA Damage ; DNA Repair ; genetics ; DNA Repair Enzymes ; genetics ; Dihydroxydihydrobenzopyrenes ; urine ; Extraction and Processing Industry ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Humans ; Lymphocytes ; Male ; Micronucleus Tests ; Middle Aged ; Occupational Exposure ; analysis ; Polymorphism, Genetic ; Smoking

OBJECTIVETo investigate the DNA and chromosome damage in peripheral blood lymphocyte of workers occupationally exposed to formaldehyde (FA).

METHODSAll 151 workers occupationally exposed to FA from two plywood factories and 112 workers without occupational FA exposure working in a machine manufactory were recruited into this study. Comet assay and cytokinesis-block micronucleus technique was used to evaluate the DNA and chromosomal damage of peripheral blood lymphocyte. The air FA samples were collected with SKC 224-PCXR8 air samplers. Gas chromatography was used to analyze the FA level. Personal information including occupational history, age, sex, smoking and drinking status was collected by the questionnaire.

RESULTSThe time weighted average concentration (TWA) of FA in the working environment of FA-exposed workers (range 0.10 - 7.88 mg/m(3)) was higher than those in controls (< 0.01 mg/m(3)). The olive tail moment (Olive TM) in low FA-exposed workers [3.03 (2.49 - 3.67)] was lower than that in high FA-exposed workers [3.95 (3.53 - 4.43)], but higher than that in controls [0.93 (0.78 - 1.10)], the differences were statistical significant (P < 0.05). Comet trail length in FA-exposed workers were significantly higher than that in controls [6.78 (6.05 - 7.60)], but no significant differences ware found between the high FA-exposed workers [12.59 (11.80 - 13.43)] and the low FA-exposed workers [11.25 (10.12 - 12.50)]. The frequency of micronuclei per 100 binucleated cells in low FA-exposed workers (0.41 +/- 0.25) was lower than that in high FA-exposed workers (0.65 +/- 0.36), but higher than that in controls (0.27 +/- 0.13), the differences were statistical significant (P < 0.05). The increased tendencies with the exposure levels were found in those three indices. In stratification analysis, the same results were found.

CONCLUSIONIn the current FA exposure levels, the DNA and chromosomal damage in peripheral blood lymphocyte might be induced by FA exposure, and be increased with the levels of exposure.

Adult ; Alcohol Drinking ; Comet Assay ; DNA Damage ; Formaldehyde ; analysis ; poisoning ; Humans ; Lymphocytes ; drug effects ; metabolism ; Micronucleus Tests ; Occupational Exposure ; analysis ; Smoking ; Young Adult

OBJECTIVETo investigate the association of polymorphisms of metabolic and DNA repair enzyme genes and DNA damage in peripheral blood lymphocytes in coke-oven workers.

METHODSOne 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.

RESULTSIn 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, P < 0.01). 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).

CONCLUSIONXRCC1 and GSTP1 polymorphisms might influence the susceptibility of DNA damage in occupational PAH-exposed coke-oven workers.

Adult ; Case-Control Studies ; Coke ; poisoning ; Comet Assay ; Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; DNA Damage ; DNA Ligase ATP ; DNA Ligases ; genetics ; DNA Repair Enzymes ; genetics ; Female ; Genotype ; Glutathione S-Transferase pi ; genetics ; Humans ; Logistic Models ; Male ; Middle Aged ; Multivariate Analysis ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Occupational Exposure ; adverse effects ; analysis ; Polymorphism, Genetic

OBJECTIVETo investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers.

METHODSThe 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.

RESULTSThe geometric means of urinary 1-hydroxypyrene levels in coke-oven workers and the controls were 12.0 and 0.7 micromol/mol Cr respectively (P < 0.01). 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)%, P < 0.01. The haplotype CGGG was associated with the decreased frequencies of total micronucleus, and the haplotypes TGGG (P = 0.01) and CGAG (P < 0.05) were associated with the increased frequencies of total micronucleus in the multivariate analysis with adjustment for covariates among coke-oven workers.

CONCLUSIONSThe genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.

Adult ; China ; Chromosome Breakage ; Coke ; poisoning ; DNA-Binding Proteins ; genetics ; Female ; Genetic Predisposition to Disease ; Haplotypes ; Humans ; Lymphocytes ; metabolism ; Male ; Micronucleus Tests ; methods ; Middle Aged ; Occupational Diseases ; etiology ; genetics ; urine ; Occupational Exposure ; adverse effects ; analysis ; Polymorphism, Single Nucleotide ; Pyrenes ; analysis ; X-ray Repair Cross Complementing Protein 1

OBJECTIVETo investigate the immunological mechanism of allergic dermatitis induced by trichloroethylene (TCE).

METHODSThe guinea pig model of TCE-induced allergic dermatitis was established by Guinea pig Maximization Test. The effects of TCE and its metabolites on splenic lymphocytes of TCE-sensitized and non-sensitized guinea pig were detected by MTT assay.

RESULTSFor TCE-sensitized guinea pig, the survival rate of lymphocytes cultured with TCE (+S9) was significantly higher than that cultured with TCE (-S9) (83.0% +/- 3.4% vs 75.9% +/- 7.9%, P < 0.01), while, for normal animals, the survival rate of lymphocytes cultured with TCE (+S9) was significantly lower than that cultured with TCE (-S9) (63.4% +/- 8.4% vs 77.0% +/- 7.2%, P < 0.01). The survival rate of lymphocytes cultured with TCE (+S9) in TCE-sensitized animals was higher than that in normal animals (83.0% +/- 3.4% vs 63.4% +/- 8.4%, P < 0.05), but no statistically significant difference was found for TCE (-S9) (75.9% +/- 7.9% vs 77.0% +/- 7.2%, P > 0.05).

CONCLUSIONCytotoxicity of TCE to normal lymphocytes and proliferation of sensitized lymphocytes were enhanced by metabolic activation. The metabolites of TCE may act as effective immune hapten to stimulate the proliferation of hapten-specific lymphocytes in TCE-sensitized animals.

Animals ; Cell Proliferation ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Dermatitis, Allergic Contact ; etiology ; immunology ; Female ; Guinea Pigs ; Lymphocytes ; drug effects ; Male ; Passive Cutaneous Anaphylaxis ; drug effects ; Spleen ; drug effects ; immunology ; Trichloroethylene ; toxicity

OBJECTIVETo investigate the association between polymorphisms of metabolic enzyme genes and chromosomal damage risk in peripheral blood lymphocytes among coke oven workers.

METHODSOne 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.

RESULTSIn 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.

CONCLUSIONSignificant 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.

Adult ; DNA Damage ; genetics ; Epoxide Hydrolases ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Glutathione Transferase ; genetics ; Humans ; Logistic Models ; Lymphocytes ; metabolism ; Male ; Middle Aged ; Multivariate Analysis ; NAD(P)H Dehydrogenase (Quinone) ; genetics ; Occupational Exposure ; Polycyclic Aromatic Hydrocarbons ; poisoning ; Polymorphism, Genetic ; Pyrenes ; analysis ; Risk Factors