title: Chromosomal damage and polymorphisms of metabolic genes among 1, 3-butadiene-exposed workers in a matched study in China.
abstract: 1, 3-Butadiene (BD) is a high-efficiency carcinogen in rodents and was classified as a human carcinogen in 2008 by the International Agency for Research on Cancer. However, its ability to induce genetic damage and the influence of metabolic polymorphisms to such damage in humans are both controversial claims. This study was conducted to investigate the relationships between exposure to BD, the polymorphisms of metabolic genes and the chromosomal damage in 45 pairs of occupationally exposed workers in a BD product workshop and matched control workers in an administrative office and circulatory water workshop in China. Exposure to BD was evaluated by personal sampling and stationary sampling. Different chromosomal damage endpoints in peripheral blood lymphocytes were determined using the cytokinesis-blocked micronucleus (CBMN) cytome assay; polymorphisms of metabolic genes [cytochrome P450 2E1 (CYP2E1), glutathione S-transferases (GST) and microsomal epoxide hydrolase (mEH)] in BD-exposed group were detected by polymerase chain reaction (PCR) or PCR-restriction fragment length polymorphism analysis. The results show that the average BD measurements of the exposed group were significantly higher than those for the control group (a personal sampling and stationary sampling, respectively). The BD-exposed workers exhibited increased frequencies of micronuclei (MNi) (8.00 ± 3.78‰ versus 5.62 ± 2.41‰) and nucleoplasmic bridges (NPBs) (2.58 ± 2.79‰ versus 1.13 ± 1.34‰) and a decreased nuclear division index (2.20 ± 0.14 versus 2.35 ± 0.27) when compared subjects in the control group. Meanwhile, BD-exposed workers carrying CYP2E1 c1c2/c2c2 or mEH intermediate (I)/high (H) group had a significantly higher NPB frequency than those carrying CYP2E1 c1c1 [frequency ratio (FR) = 2.60, 95% confidence interval (CI) 1.72-3.93; P < 0.0001) or the mEH low(S) group (FR = 2.06, 95% CI% 1.17-3.62; P < 0.05), respectively. Our study suggests that MNi and NPB frequency in CBMN cytome assay could be potential genotoxic biomarkers for BD exposure in humans. The polymorphism of CYP2E1 and mEH could also affect the chromosomal instability of BD workers.
authors.affiliation: Department of Hygiene Toxicology, College of Preventive Medicine, Third Military Medical University, 30 Gao TanYan, Chongqing 400038, People's Republic of China.
authors.forename: Menglong
authors.initials: M
authors.lastname: Xiang
authors.forename: Lin
authors.initials: L
authors.lastname: Ao
authors.forename: Huan
authors.initials: H
authors.lastname: Yang
authors.forename: Wenbin
authors.initials: W
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Sun
authors.forename: Xue
authors.initials: X
authors.lastname: Han
authors.forename: Daibo
authors.initials: D
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Cui
authors.forename: Niya
authors.initials: N
authors.lastname: Zhou
authors.forename: Jingyi
authors.initials: J
authors.lastname: Liu
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
mesh_terms: D000328:Adult; D002070:Butadienes / Q000009:adverse effects*; D016022:Case-Control Studies; D002681:China; D043171:Chromosomal Instability; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D004249:DNA Damage / Q000187:drug effects; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D008875:Middle Aged; D009153:Mutagens / Q000009:adverse effects*; D016273:Occupational Exposure / Q000009:adverse effects; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D002070:Butadienes; D009153:Mutagens; D019392:Cytochrome P-450 CYP2E1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C031763:1,3-butadiene