Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells
Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells
复制标题
苯并(a)芘诱导人肺腺癌细胞H1299 p73 mRNA表达和坏死
DOI：
10.1002/tox.20631
复制
发表时间：
2012-03-01
影响因子：
4.5
通讯作者：
Yuan, Jing
中科院分区：
文献类型：
--
作者：
Jiang, Ying;Rao, Kaimin;Yuan, Jing
p53可介导苯并（a）芘（BaP）诱导的多种细胞系DNA损伤诱导的凋亡。然而，p53家族成员之一的p73在BaP诱导的凋亡性细胞死亡中的潜在作用仍有待确定。在这项研究中，正常胎儿肺成纤维细胞（MRC-5）和人肺腺癌细胞（H1299，p53-null）与BaP在8，16，32，64，和128 μ M的浓度处理4和12小时。检测氧化应激状态、DNA损伤程度、p53、p73、mdm 2、bcl-2和bax在mRNA和蛋白水平的表达以及凋亡和/或坏死的百分比。在这两个BaP处理的细胞系，我们观察到增加丙二醛（MDA）的形成和减少超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）的活性在4小时后的治疗，此外，在4和12小时的时间点，我们观察到极高水平的DNA损伤。此外，BaP作用4 h后可诱导MRC-5和H1299细胞坏死，但可抑制MRC-5细胞凋亡（均P < 0.01）。此外，在BaP处理的H1299细胞中，仅p73 mRNA水平上调。结果表明，BaP诱导的DNA损伤可以触发从凋亡性细胞死亡向坏死性细胞死亡的转变，并且在这些细胞系中，坏死性细胞死亡不依赖于p53和p73。未来的研究需要在更多的细胞系中研究BaP诱导的细胞死亡类型变化的时间过程。(C)2010 Wiley Periodicals，Inc.环境毒理学，2012年。
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 mu M 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. (C) 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.