Biomarkers and Molecular Epidemiological Study among Workers Exposed to PAHs

摘要

Exploring the associations between genetic polymorphisms of metabolic enzymes and susceptibility to PAH-induced chromosomal damage is of great significance for understanding PAH carcinogenesis. CYP450s, GSTs, mEH, NQO and NAT 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 μmol/mol Creat respectively (P < 0.01). The CBMN frequency (number of MN per 1000 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), P < 0.01). Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His_(113) variant genotype exhibited significantly lower CBMN frequency (8.5 ± 6.5 (per thousand)) than did the Tyr_(11.3)/Tyr~(113) genotype (11.3 ± 6.4 (per thousand), P < 0.01); 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 Val_(105)/Val_(105) genotype exhibited a higher CBMN frequency (15.0 ± 5.8 (per thousand)) than did the GSTP1 Ile_(105)/Ile_(105) or Ile_(105)/Val_(105) genotypes (9.3 ± 6.5 (per thousand), P < 0.01); 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.