Genetic polymorphisms of XRCC1, HOGG1 and MGMT and micronucleus occurrence in Chinese vinyl chloride-exposed workers.
In this study, a group of 313 workers occupationally exposed to vinyl chloride monomer (VCM) and 141 normal unexposed referents were examined for chromosomal damage using the cytokinesis-blocked micronucleus (CBMN) assay in peripheral lymphocytes. We explored the relationship between genetic polymorphisms of XRCC1 (Arg194Trp, Arg280His and Arg399Gln), MGMT(Leu84Phe) and hOGG1 (Ser326Cys) and susceptibility of chromosomal damage induced by VCM. Polymerase chain reaction-restriction fragment length polymorphism techniques were used to detect polymorphisms in XRCC1, hOGG1 and MGMT. It was found that the micronuclei (MN) frequency of exposed workers (4.86 +/- 2.80) per thousand was higher than that of the control group (1.22 +/- 1.24) per thousand (P < 0.01). Increased susceptibility to chromosomal damage as evidenced by higher MN frequency was found in workers with hOGG1 326 Ser/Cys genotype [frequency ratio (FR) = 1.21, 95% confidence interval (CI): 1.02-1.46; P < 0.05], XRCC1 194 Arg/Trp (FR = 1.12, 95% CI: 1.00-1.25; P < 0.05) and XRCC1 280 Arg/His and His/His genotypes (FR = 1.12, 95% CI 1.00-1.26, P < 0.05). Moreover, among susceptibility diplotypes, CGA/CAG carriers had more risk of MN frequency compared with individuals with wild-type CGG/CGG (FR = 1.67, 95% CI: 1.19-2.23; P < 0.05). MN frequency also increased significantly with age in the exposed group (FR = 1.13, 95% CI: 1.00-1.28; P < 0.05). Thus, CB-MN was a sensitive index of early damage among VCM-exposed workers. Genotype XRCC1 Arg194Trp, Arg280His, hOGG1 Ser326Cys, diplotype CGA/CAG and higher age may have an impact on the chromosome damage induced by VCM.
Wang
Qi
Q
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, and Key laboratory of public health and safety of Ministry of Education of China, 138 Yixue yuan Road, Shanghai, 200032,China.
Ji
Fang
F
Sun
Yuan
Y
Qiu
Yu-Lan
YL
Wang
Wei
W
Wu
Fen
F
Miao
Wen-Bin
WB
Li
Yongliang
Y
Brandt-Rauf
Paul W
PW
Xia
Zhao-Lin
ZL
D000328:Adult; D001483:Base Sequence; D002681:China; D045647:DNA Glycosylases / Q000235:genetics*; D015254:DNA Modification Methylases / Q000235:genetics*; D017931:DNA Primers; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D016273:Occupational Exposure; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D014752:Vinyl Chloride / Q000633:toxicity*; D000076105:X-ray Repair Cross Complementing Protein 1
D017931:DNA Primers; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D045643:DNA Repair Enzymes; D014752:Vinyl Chloride