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Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells
Author(s) -
Jiang Ying,
Rao Kaimin,
Yang Guangtao,
Chen Xi,
Wang Qian,
Liu Ailin,
Zheng Hongyan,
Yuan Jing
Publication year - 2012
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20631
Subject(s) - apoptosis , microbiology and biotechnology , benzo(a)pyrene , programmed cell death , oxidative stress , dna damage , necrosis , malondialdehyde , superoxide dismutase , chemistry , cell culture , glutathione peroxidase , glutathione , biology , andrology , carcinogen , biochemistry , dna , medicine , enzyme , genetics
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. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.