title: 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.
abstract: 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 c (cyt c) 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 (ΔΨ(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 ΔΨ(m), up-regulation of p53 and down-regulation of c-Myc, but independent of the opening of mPTP in 16HBE cells.
authors.affiliation: Division of Preventive Medicine, Tongji University Medical School, 1239 Siping Road, Shanghai 200092, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Sang
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhang
authors.forename: Jue
authors.initials: J
authors.lastname: Li
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D055745:Bronchioles / Q000166:cytology / Q000187:drug effects*; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*
chemical_list: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D045304:Cytochromes c