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

¹ National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China and ² Institute of Industrial Health, Benxi Steel Industrial Corp., Benxi, Liaoning, China

Requests for reprints: Yuxin Zheng, National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing, China 100050. Phone: 86-10-83132515; Fax: 86-10-63182372. E-mail: yxzheng{at}163bj.com

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.

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