Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers

Abstract

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 μmol/mol creatinine, respectively (P < 0.01). The CBMN frequency (number of micronuclei per 1,000 binucleated lymphocytes) was significantly higher in coke-oven workers (9.5 ± 6.6‰) than in the controls (4.0 ± 3.6‰; P < 0.01). 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‰) than did the Tyr113/Tyr113 genotype (11.3 ± 6.4‰; P < 0.01); the low mEH activity phenotype exhibited a lower CBMN frequency (8.6 ± 6.8‰) than did the high mEH activity phenotype (13.2 ± 6.7‰; P = 0.01); the GSTP1 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 ± 5.8‰) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 genotypes (9.3 ± 6.5‰; 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.