Prevalence and persistence of chromosomal damage and susceptible genotypes of metabolic and DNA repair genes in Chinese vinyl chloride-exposed workers.
Vinyl chloride (VC) was classified as a group 1 carcinogen by IARC in 1987. Although the relationship between VC exposure and liver cancer has been established, the mechanism of VC-related carcinogenesis remains largely unknown. Previous epidemiological studies have shown that VC exposure is associated with increased genotoxicity in humans. To explore chromosomal damage and its progression, and their association to genetic susceptibility, we investigated 402 workers exposed to VC, a 77 VC-exposed cohort and 141 unexposed subjects. We measured the frequencies of cytokinesis-block micronucleus (CBMN) to reflect chromosomal damage and conducted genotyping for six xenobiotic metabolisms and five DNA repair genes' polymorphism. Data indicate that 95% of the control workers had CBMN frequencies </=3 per thousand, whereas VC-exposed workers had the 3.73-fold increase compared with the controls. Among the cohort workers who were followed from 2004 to 2007, the mean CBMN frequency was higher in 2007 than in 2004 with ratio of 2.08. Multiple Poisson regression analysis showed that mean CBMN frequencies were significantly elevated for the intermediate and high exposure groups than the low. Exposed workers with CYP2E1 or XRCC1 variance showed a higher CBMN frequency than their wild-type homozygous counterparts, so did workers with GSTP1 or ALDH2 genotype. This study provides evidence that cumulative exposure dose of VC and common genetic variants in genes relevant to detoxification of carcinogens are the major factors that modulate CBMN induction in VC-exposed workers.
Ji
Fang
F
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, China.
Wang
Wei
W
Xia
Zhao-Lin
ZL
Zheng
Ying-Jia
YJ
Qiu
Yu-Lan
YL
Wu
Fen
F
Miao
Wen-Bin
WB
Jin
Ru-Feng
RF
Qian
Ji
J
Jin
Li
L
Zhu
Yi-Liang
YL
Christiani
David C
DC
D000328:Adult; D044466:Asian People / Q000235:genetics; D002875:Chromosomes / Q000187:drug effects*; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D008875:Middle Aged; D016273:Occupational Exposure; D016012:Poisson Distribution; D013997:Time Factors; D014752:Vinyl Chloride / Q000633:toxicity
D014752:Vinyl Chloride