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 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.

• Authors: Shuguang Leng, Yufei Dai, Yong Niu, Zufei Pan, Xiaohua Li, Juan Cheng, Fengsheng He, Yuxin Zheng
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 13 Issue 10 Pg. 1631-9 (Oct 2004) ISSN: 1055-9965 [Print] United States
• PMID: 15466980 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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