Effects of genetic polymorphisms of metabolic enzymes on cytokinesis-block micronucleus in peripheral blood lymphocyte among coke-oven workers.
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.
Leng
Shuguang
S
National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, 29 Nanwei Road, Beijing, 100050.
Dai
Yufei
Y
Niu
Yong
Y
Pan
Zufei
Z
Li
Xiaohua
X
Cheng
Juan
J
He
Fengsheng
F
Zheng
Yuxin
Y
D000217:Acyltransferases / Q000235:genetics* / Q000494:pharmacology; D000328:Adult; D003077:Coke; D048749:Cytokinesis; D004249:DNA Damage; D004851:Epoxide Hydrolases / Q000235:genetics* / Q000494:pharmacology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D017745:Incineration; D008214:Lymphocytes; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D016273:Occupational Exposure; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning*; D011110:Polymorphism, Genetic
D000217:Acyltransferases; D003077:Coke; D004851:Epoxide Hydrolases; D005982:Glutathione Transferase; D011084:Polycyclic Aromatic Hydrocarbons; C043403:fatty acyl ethyl ester synthase