title: Genetic damage induced by organic extract of coke oven emissions on human bronchial epithelial cells.
abstract: Coke oven emissions are known as human carcinogen, which is a complex mixture of polycyclic aromatic hydrocarbon. In this study, we aimed to clarify the mechanism of action of coke oven emissions induced carcinogenesis and to identify biomarkers of early biological effects in a human bronchial epithelial cell line with CYP1A1 activity (HBE-CYP1A1). Particulate matter was collected in the oven area on glass filter, extracted and analyzed by GC/MS. DNA breaks and oxidative damage were evaluated by alkaline and endonucleases (FPG, hOGG1 and ENDO III)-modified comet assays. Cytotoxicity and chromosomal damage were assessed by the cytokinesis-block micronucleus cytome (CBMN-Cyt) assay. The cells were treated with organic extract of coke oven emissions (OE-COE) representing 5, 10, 20, 40μg/mL extract for 24h. We found that there was a dose-effect relationship between the OE-COE and the direct DNA damage presented by tail length, tail intensity and Olive tail moment in the comet assay. The presence of lesion-specific endonucleases in the assays increased DNA migration after OE-COE treatment when compared to those without enzymes, which indicated that OE-COE produced oxidative damage at the level of pyrimidine and purine bases. The dose-dependent increase of micronuclei, nucleoplasmic bridges and nuclear buds in exposed cells was significant, indicating chromosomal and genomic damage induced by OE-COE. Based on the cytotoxic biomarkers in CBMN-Cyt assay, OE-COE may inhibit nuclear division, interfere with apoptosis, or induce cell necrosis. This study indicates that OE-COE exposure can induce DNA breaks/oxidative damage and genomic instability in HBE-CYP1A1 cells. The FPG-comet assay appears more specific for detecting oxidative DNA damage induced by complex mixtures of genotoxic substances.
authors.affiliation: Faculty of Public Health, Weifang Medical University, 7166 Baotongwest street, Weifang 261053, PR China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Zhai
authors.forename: Huawei
authors.initials: H
authors.lastname: Duan
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Chuanfeng
authors.initials: C
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Niu
authors.forename: Yufei
authors.initials: Y
authors.lastname: Dai
authors.forename: Ping
authors.initials: P
authors.lastname: Bin
authors.forename: Qingjun
authors.initials: Q
authors.lastname: Liu
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Junxiang
authors.initials: J
authors.lastname: Ma
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003077:Coke; D020552:Comet Assay; D045424:Complex Mixtures / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004249:DNA Damage; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D003077:Coke; D045424:Complex Mixtures; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1