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

Journal Article · · Cancer Epidemiology, Biomarkers and Prevention
OSTI ID:20823744
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  1. Chinese Center for Disease Control and Prevention, Beijing (China). National Institute for Occupational Health and Poison Control

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 {mu}mol/mol creatinine, respectively. 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. Among the coke-oven workers, age was positively associated with CBMN frequency; the mEH His{sup 113} variant genotype exhibited significantly lower CBMN frequency than did the Tyr{sup 113}/Tyr{sup 113} genotype; the low mEH activity phenotype exhibited a lower CBMN frequency than did the high mEH activity phenotype; the GSTP1 Val{sup 105}/Val{sup 105} genotype exhibited a higher CBMN frequency than did the GSTP1 Ile{sup 105}/Ile{sup 105} or Ile{sup 105}/Val{sup 105} genotypes; 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.

OSTI ID:
20823744
Journal Information:
Cancer Epidemiology, Biomarkers and Prevention, Vol. 13, Issue 10; ISSN 1055-9965
Country of Publication:
United States
Language:
English