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

Cancer Epidemiol Biomarkers Prev. 2004 Oct;13(10):1631-9.

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 micromol/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 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 His113 variant genotype exhibited significantly lower CBMN frequency (8.5 +/- 6.5 per thousand) than did the Tyr113/Tyr113 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 Val105/Val105 genotype exhibited a higher CBMN frequency (15.0 +/- 5.8 per thousand) than did the GSTP1 Ile105/Ile105 or Ile105/Val105 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics*
  • Acyltransferases / pharmacology
  • Adult
  • Coke
  • Cytokinesis
  • DNA Damage*
  • Epoxide Hydrolases / genetics*
  • Epoxide Hydrolases / pharmacology
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Glutathione Transferase / genetics*
  • Glutathione Transferase / pharmacology
  • Humans
  • Incineration
  • Lymphocytes
  • Male
  • Micronuclei, Chromosome-Defective
  • Middle Aged
  • Occupational Exposure*
  • Polycyclic Aromatic Hydrocarbons / poisoning*
  • Polymorphism, Genetic*

Substances

  • Coke
  • Polycyclic Aromatic Hydrocarbons
  • Acyltransferases
  • Glutathione Transferase
  • glutathione S-transferase M1
  • fatty acyl ethyl ester synthase
  • Epoxide Hydrolases