Genetic polymorphisms of DNA repair genes and chromosomal damage in workers exposed to 1,3-butadiene

Q Wang, A. h Wang, H. s Tan, N. n Feng, Y. j Ye, X. q Feng, G Liu, Y. x Zheng and Z. l. Xia

Carcinogenesis, 2010, 31(5), 858-863. DOI: 10.1093/carcin/bgq049

Abstract

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) was higher than that of the non-exposed groups (1.48 ± 1.26) (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.

ASCI-ID: 1078-341