Biomarkers Of Dna Damage And Repair Among Workers Exposed To 1,3-butadiene

1,3-butadiene (BD) is widely used in petrochemical industry and manufacture, such as the production of rubber, balsam, plastic material. Epidemiological studies display that occupational exposure to BD is associated with the increased risk of leukemia and lymphatics. The carcinogenicity of BD to rodent has been proved, but its probably carcinogenicity and molecular mechanism(s) of mutagenicity are not fully elucidated in humans. It's difficult to evaluate BD using relatively insensitive traditional epidemiological studies due to the reduced threshold limit to BD; fortunately, DNA damage and repair are the important biological events of carcinogenesis. In this study, we investigate the biomarkers of DNA damage and repair to understand the carcinogenesis of BD and improve the risk assessment.To meet the requirement in the prevention of workers, we conducted the study. The study hypothesis is to investigate the association of chromosome damage, DNA repair capacity and polymorphisms of methylenetetrahydrofolate reductase and DNA repair genes among BD-exposed workers. A cross-sectional molecular epidemiological design was conduced to testify this hypothesis. The main results are as follows:1. Association between polymorphisms of DNA double-strand break (DSBR) pathway genes and chromosome damage in peripheral blood lymphocytes detected by cytokinesis-block micronucleus (CBMN) among 189 BD-exposed workers and 83 controls were determined. Multivariate analysis of covariance revealed that in BD-exposed workers, the X-ray repair cross- complementing group4(XRCC4) A245G polymorphism, AA genotype exhibited significantly higher NPB frequency (1.00(0.92-1.75)‰) than did the GG (0.00(0.01-1.68)‰, P=0.02). For the methylenetetrahydrofolate reductase(MTHFR) AA genotype of A1298C polymorphism exhibited significantly lower CBMN frequency (6.16±5.06‰) than did the AC (8.02±5.57‰, P=0.04) or AC+CC genotypes (8.12±5.58‰, P=0.03).2. DNA repair capacity (DRC) in peripheral blood lymphocytes among 60 BD-exposed workers and 60 non-exposed controls was measured by the repair rate of bleomycin-induced DNA damage using an chromatid breaks assay. Chromosome damage in peripheral blood lymphocytes detected by CBMN assay and the polymorphisms of X-ray repair cross-complementing group 4 (XRCC4) were genotyped by PCR-RFLP method. The chromatid breaks per cell(b/c) were higher in BD-exposed workers than in controls (1.06±0.41‰vs. 0.85±0.36‰, P<0.01) significantly.The level of b/c was significant lower in BD-exposed workers with AG+GG genotype of A245G polymorphism of XRCC4 than those with AA genotype (0.97±0.33‰vs. 1.18±0.48‰,P=0.03). For the XRCC4 T1394G polymorphism, GG genotype exhibited significantly higher b/c (1.13±0.42‰) than did the TT genotype (1.13±0.42‰,P=0.04). There were significant correlations between the level of DRC and CBMN frequencies among BD-exposed workers (n = 60, R= -0.709, P=0.039) or whole subjects (n =120, R= - 0.685, P<0.001), but not in control group (n = 60, R= - 0.680, P=0.155).In present study, the increased chromosome damage and decreased DNA repair capacity were important biological events for BD carcinogenesis. This will be of great importance for understanding of BD carcinogenesis and individual susceptibility which would facilitate developing biomarkers for improvement of risk assessment.