title: Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells.
abstract: p53 can mediate DNA damage-induced apoptosis in various cell lines treated with Benzo(a)pyrene (BaP). However, the potential role of p73, one of the p53 family members, in BaP-induced apoptotic cell death remains to be determined. In this study, normal fetal lung fibroblasts (MRC-5) and human lung adenocarcinoma cells (H1299, p53-null) were treated with BaP at concentrations of 8, 16, 32, 64, and 128 μM for 4 and 12 h. The oxidative stress status, extent of DNA damage, expression of p53, p73, mdm2, bcl-2, and bax at the mRNA and protein levels, and the percentages of apoptosis and/or necrosis were assessed. In the two BaP-treated cell lines, we observed increased malondialdehyde (MDA) formation and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity at 4 h after the treatment; furthermore, at the time points of 4 and 12 h, we observed extremely high levels of DNA damage. In addition, at 4 h after the treatment, BaP had induced necrosis in MRC-5 and H1299 cells, but it had inhibited apoptosis in MRC-5 cells (P < 0.01 for all). Furthermore, in BaP-treated H1299 cells, only the p73 mRNA level was up-regulated. The results suggested that BaP-induced DNA damage could trigger a shift from apoptotic cell death toward necrotic cell death and that necrotic cell death is independent of p53 and p73 in these cell lines. Future studies are needed to investigate the time course of changes in the type of BaP-induced cell death in more cell lines.
authors.affiliation: Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Kaimin
authors.initials: K
authors.lastname: Rao
authors.forename: Guangtao
authors.initials: G
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Ailin
authors.initials: A
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zheng
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002460:Cell Line; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D009336:Necrosis / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014158:Transcription, Genetic; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D001564:Benzo(a)pyrene