Effects of Genetic Polymorphisms of Metabolic Enzymes on Cytokinesis-Block Micronucleus in Peripheral Blood Lymphocyte among Coke-Oven Workers

Abstract

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.