title: Genetic variations of CYP2B6 gene were associated with plasma BPDE-Alb adducts and DNA damage levels in coke oven workers.
abstract: Polycyclic aromatic hydrocarbons (PAHs), the main components of coke oven emissions, can induce activation of cytochrome P450 (CYP) enzymes, which metabolize PAHs and result in DNA damage by forming adducts. This study was designed to know whether genetic variants of CYP genes are associated with plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts and DNA damage in coke oven workers. In this study, 298 workers were divided into four groups according to the environmental PAHs exposure levels. The concentrations of plasma BPDE-Alb adducts were detected by reverse-phase high-performance liquid chromatography and the DNA damage levels were measured using comet assay. Twelve tag single nucleotide polymorphisms (tagSNPs) of 4 CYP genes were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the top group, workers with CYP2B6 rs3760657GA genotype have lower BPDE-Alb adducts and DNA damage levels than those with rs3760657GG genotype (P<0.05). In the control group, the DNA damage levels of subjects with CYP1A1 rs4646421AA or GA+AA genotypes were lower than those with GG genotype (P<0.05). However, no such effects were shown for the other tagSNPs. These results suggested that genetic variations of CYP2B6 might be associated with low BPDE-Alb adducts and DNA damage levels in worker with high exposure to PAHs.
authors.affiliation: Institute of Occupational Medicine and Ministry of Education Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13 Hangkong Rd, Wuhan, Hubei 430030, China.
authors.forename: Guoxiang
authors.initials: G
authors.lastname: Huang
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity*; D000328:Adult; D000418:Albumins / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D003077:Coke; D020552:Comet Assay; D065702:Cytochrome P-450 CYP2B6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D018736:DNA Adducts / Q000187:drug effects / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008669:Metallurgy; D016273:Occupational Exposure / Q000009:adverse effects*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects; D013232:Steel
chemical_list: D000418:Albumins; D002273:Carcinogens; D003077:Coke; D018736:DNA Adducts; D013232:Steel; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D010089:Oxidoreductases, N-Demethylating