Genetic polymorphisms of DNA repair genes and chromosomal damage in workers exposed to 1,3-butadiene.
The base excision repair (BER) pathway is important in repairing DNA damage incurred from occupational exposure to 1,3-butadiene (BD). This study examines the relationship between inherited polymorphisms of the BER pathway (x-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg280His, Arg399Gln, T-77C, ADPRT Val762Ala, MGMT Leu84Phe and APE1 Asp148Glu) and chromosomal damage in BD-exposed workers, using the cytokinesis-blocked (CB) micronucleus (MN) assay in peripheral lymphocytes of 166 workers occupationally exposed to BD and 41 non-exposed healthy individuals. The MN frequency of exposed workers (3.39 +/- 2.42) per thousand was higher than that of the non-exposed groups (1.48 +/- 1.26) per thousand (P < 0.01). Workers receiving greater than median annual BD exposures had higher MN values than lower exposed workers: frequency ratio (FR) of 1.30, 95% confidence interval (CI) 1.14-1.53; P < 0.05. Workers who carried the following genotypes were associated with greater frequency of MN (P < 0.05 for each comparison, unless specified): XRCC1 -77 C/T genotype (FR = 1.28, 95% CI: 1.04-1.57; reference C/C), ADPRT 762 Ala/Ala (FR = 1.54, 95% CI: 1.17-2.03; P < 0.01), XRCC1 194 Arg/Trp (FR = 1.13, 95% CI: 0.87-1.27; reference, Arg/Arg), XRCC1 280 Arg/His (FR = 1.67, 95% CI: 1.10-2.42; reference, Arg/Arg), XRCC1 399 Arg/Gln and Gln/Gln genotypes (FR = 1.26, 95% CI: 1.03-1.53 and FR = 1.24, 95% CI 1.03-1.49; reference Arg/Arg, respectively). As XRCC1 polymorphisms were linked, workers carrying the XRCC1 (-77)-(194)-(280)-(399) diplotype, TCGA/TCGA, had a higher MN frequency compared with individuals carrying the wild-type CCGG/CCGG (FR = 1.57, 95% CI: 1.02-2.41; P < 0.05). In conclusion, CB-MN is a sensitive index of early damage among BD-exposed workers. In workers exposed to BD, multiple BER polymorphisms and a XRCC1 haplotype were associated with differential levels of chromosome damage.
Wang
Qi
Q
Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Key Laboratory of Public Health and Safety of Ministry of Education of China, Shanghai 200032, China.
Wang
Ai-hong
AH
Tan
Hong-shan
HS
Feng
Nan-nan
NN
Ye
Yun-jie
YJ
Feng
Xiao-qing
XQ
Liu
Geoffrey
G
Zheng
Yu-xin
YX
Xia
Zhao-lin
ZL
D000328:Adult; D002070:Butadienes / Q000633:toxicity*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D008875:Middle Aged; D016273:Occupational Exposure; D016012:Poisson Distribution; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D000076105:X-ray Repair Cross Complementing Protein 1
D002070:Butadienes; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; C031763:1,3-butadiene