Anti-benzopyrene-7,8-diol-9,10-epoxide induces apoptosis via mitochondrial pathway in human bronchiolar epithelium cells independent of the mitochondria permeability transition pore

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• 作者：Hao Sang¹ ; Lijuan Zhang¹ ; ^{zhangxiaoyi@tongji.edu.cn} ; Jue Li ; ^{jueli@tongji.edu.cn}
• 关键词：16HBE ; human bronchiolar epithelium cells ; 螖唯m ; mitochondrial membrane potential ; B[a]P ; benzo[a]pyrene ; BPDE ; anti-benzo[a]pyrene-7 ; 8-diol-9 ; 10-epoxide ; cyt c ; cytochrome c ; DCFH-DA ; 2&prime ; 7&prime ; -dichloro-cluorescein diacetate ; DMSO ; dimethyl sulf
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：July, 2012
• 卷：50
• 期：7
• 页码：2417-2423
• 文件大小：1098 K

摘要

Anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a ubiquitous environmental pollutant contained in tobacco smoke, automobile exhausts and barbecued foods. The carcinogenicity of BPDE on animals has been well characterized, whereas its apoptotic effect is not well defined. A recent study has shown that BPDE-mediated apoptotic pathway has varying specificity across different cell lines. Squamous cell carcinoma (SCC) arises from bronchiolar epithelium cells, therefore, we set out to investigate the pulmonary toxicity and apoptotic effect of BPDE in human bronchiolar epithelium cells (16HBE). Our results show BPDE induces mitochondrial-mediated apoptosis in a dose-dependent manner in 16HBE cells. The cleavage of caspase-3,-9 and release of Cytochrome m>cm> (cyt m>cm>) was regulated during apoptotic stimulation. However, the opening of mitochondria permeability transition pore (mPTP) has not been detected. Furthermore, our data also indicate that the formation of reactive oxygen species (ROS), decline of mitochondrial membrane potential (螖m>唯m>_m), increasing p53 and decreasing c-Myc levels play important roles in response to BPDE toxicity. In conclusion, these results suggest that BPDE-mediated apoptosis occurs via caspase-9 dependent mitochondria pathway associated with ROS formation, loss of 螖m>唯m>_m, up-regulation of p53 and down-regulation of c-Myc, but independent of the opening of mPTP in 16HBE cells.