title: DNA repair gene deficiency does not predispose human bronchial epithelial cells to benzo(a)pyrene-induced cell transformation.
abstract: The development of cost and time-efficient in vitro assays to predict carcinogenicity of chemicals has become a very important direction for toxicological research. In this study, we generated a series of human bronchial epithelial (HBE) cells defect in DNA repair gene excision repair cross-completion 1 (ERCC1), excision repair cross-completion 2 (ERCC2), ataxia-telangiectasia mutated (ATM) and mutS homolog 2 (MSH2), respectively. The inhibition of gene expression was verified by detection of mRNA and protein levels of respective genes. The suppression of these DNA repair genes has no impact on cell proliferation or cell transformation. Although we found that the transgenic HBE cells were more sensitive in benzo(a)pyrene (BaP)-induced DNA damages measured by cytokinesis-block micronucleus (CBMN) assay and comet assay, we failed to observe enhanced effects on induction of cell transformation. HBE cells defect in DNA repair pathways did not exhibit malignantly transformed phenotype up to 20 weeks of BaP treatment, indicating that the deficiency of ERCC1, ERCC2, ATM, or MSH2 alone did not shorten the latency of cell transformation. In contrast, we found that HBE cells expressing H-Ras or c-Myc were transformed 8 or 12 weeks after BaP treatment. These findings demonstrate that silencing of a single DNA repair gene does not confer cells susceptible to chemical-induced cell transformation.
authors.affiliation: Department of Toxicology, Faculty of Preventive Medicine, Guangdong Provincial Key Laboratory of Food, Nutrition and Health, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Xing
authors.forename: Caixia
authors.initials: C
authors.lastname: Liu
authors.forename: Shifu
authors.initials: S
authors.lastname: Tang
authors.forename: Daochuan
authors.initials: D
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Chen
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Pang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zeng
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001564:Benzo(a)pyrene / Q000633:toxicity*; D001980:Bronchi / Q000166:cytology; D002273:Carcinogens / Q000633:toxicity*; D018797:Cell Cycle Proteins / Q000235:genetics; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D004847:Epithelial Cells; D020868:Gene Silencing; D006801:Humans; D051718:MutS Homolog 2 Protein / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034622:RNA Interference; D025521:Tumor Suppressor Proteins / Q000235:genetics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D002273:Carcinogens; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D001564:Benzo(a)pyrene; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C071447:ERCC1 protein, human; D004720:Endonucleases; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human