[Mutagen sensitivity in peripheral blood lymphocytes among coke-oven workers].

OBJECTIVE: To investigate the sensitivity to bleomycin (BLM) in peripheral blood lymphocytes (PBL) among coke-oven workers. METHODS: 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. RESULTS: 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, 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. CONCLUSION: 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.

[Association between methylenetetrahydrofolate reductase gene haplotypes and the susceptibility of chromosomal damage in coke-oven workers].

OBJECTIVE: To investigate the association between MTHFR gene variances and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers exposed to polycyclic aromatic hydrocarbons (PAHs). METHODS: One-hundred and forty coke-oven workers who exposed to a high level of PAHs and sixty-six non-exposed controls were selected as the study subjects. Chromosomal damage in peripheral lymphocyte was measured by the cytokinesis-block micronucleus (CBMN) assay. Urinary 1-hydroxypyrene (1-OHP) levels were measured as the internal dose of PAHs exposure. Two single nucleotide polymorphisms(SNPs) in MTHFR gene, including C677T, A1298C were detected by PCR-RFLP. The MTHFR haplotypes were estimated by Bayesian statistical method with the software of PHASE Version 2.1. The associations between haplotype pairs and CBMN were assessed by analysis of covariance in the coke-oven workers and controls. RESULTS: The variant allele frequencies for MTHFRC677T and A1298C were 0.56 and 0.16 respectively, which consistent with Hardy-Weinberg equilibrium. There was linkage disequilibrium between the two SNPs (D' = 0.99) in this study. Four haplotypes were calculated by PHASE, in terms of 677T - 1298A, 677C-1298A, 677C-1298C and 677T-1298C, the frequencies were 0.555,0.279,0.163 and 0.003 respectively. In coke-oven workers, the frequencies of total micronucleus of non-677C-1298A/677C-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.00 +/- 0.67 vs 0.60 +/- 0.41, P = 0.04). The frequencies of total micronucleus of 677T-1298A/677T-1298A haplotype pair was significantly higher than 677C-1298A/677C-1298A (1.08 +/- 0.71 vs 0.60 +/- 0.41, P = 0.04). In coke-oven workers, the frequencies of total micronucleus among the different SNPs were not significant differences, either in the controls. CONCLUSION: The haplotypes of MTHFR gene might be one genetic susceptibility factors of PAH induced chromosomal damage in coke-oven workers.

[Possible association between polymorphisms of human leukocyte antigen-DQ genes and susceptibility to trichloroethylene-induced severe generalized dermatitis].

OBJECTIVE: To investigate the association between genetic polymorphisms of human leukocyte antigen-DQ (HLA-DQ) and susceptibility to trichloroethylene (TCE)-induced severe generalized dermatitis. METHODS: 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. RESULTS: 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. CONCLUSION: The genetic polymorphisms of HLA-DQA1 might be one of the factors influencing the individual susceptibility to TCE-induced severe generalized dermatitis.

[Polymorphisms of aldehyde and alcohol dehydrogenase genes associated with susceptibility to trichloroethylene-induced medicamentosa-like dermatitis].

OBJECTIVE: Investigate the genetic polymorphisms of aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH), major enzymes involving the trichloroethylene (TCE) metabolism, associated with susceptibility to TCE-induced medicamentosa-like dermatitis. METHODS: The study included 108 patients with TCE-induced medicamentosa-like dermatitis and 145 healthy controls exposed to TCE who were engaged in the same workplace, and frequency matched by sex and age. The genotypes of ADH2, ADH3 and ALDH2 were analyzed by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP), and distribution of genotype and odds ratio were calculated. RESULTS: There were no differences in the frequencies of genotypes of ADH2 and ADH3 between cases and exposed controls. The frequency of heterozygous ALDH2 * 1/ * 2 plus homozygous ALDH2 * 2/ * 2 in cases was significantly lower than that in exposed controls (27.8% vs 43.4%, P = 0.011), and it decreased the risk of TCE-induced medicamentosa-like dermatitis (OR = 0.50, 95% CI = 0.29-0.85). CONCLUSION: The active ALDH2 might be one of the factors influencing the individual susceptibility to TCE-induced medicamentosa-like dermatitis.

[Association of XRCC1 polymorphisms and chromosomal damage levels in coke-oven workers].

OBJECTIVE: To investigate the association of XRCC1 polymorphisms and chromosomal damage levels in peripheral blood lymphocyte in coke-oven workers. METHODS: 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. RESULTS: 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 (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. CONCLUSIONS: The genetic polymorphisms of XRCC1 gene could influence the chromosome damage levels in coke-oven workers.