title: Benzo(a)pyrene-induced mitochondrial dysfunction and cell death in p53-null Hep3B cells.
abstract: Benzo(a)pyrene (BaP) has been shown to induce apoptosis and necrosis in various cell types. However, the effect of BaP on mitochondria function and p73, and their possible roles in BaP-induced cell death have not been well studied. This study focused on mitochondria-mediated cell death and the occurrence of p73 protein accumulation in BaP-treated human hepatoma Hep3B (p53-null) cells. We found that BaP (8, 16, 32 and 64μM) induced early necrosis at 12h and delayed apoptosis at 24h. BaP dramatically induced ethoxyresorufin-O-deethylase activity and led to significant increase in oxidative stress at early time points (6 and 12h). Necrotic cell death was concurrent with loss of mitochondrial membrane potential, decrease in the ATP level and activities of Na(+)/K(+)-ATPase and Ca(2+)/Mg(2+)-ATPase. However, these changes were reversed in the process of apoptosis. In addition, after BaP treatment, c-Jun N-terminal kinase (JNK) and Bax were activated during apoptosis and no change in p73 protein level was observed. These results revealed that the cells with mitochondria dysfunction and ATP depletion underwent necrosis at early time point and apoptosis afterward when they recovered from mitochondrial dysfunction and ATP depletion. Activation of JNK and Bax possibly contributed to BaP-induced apoptosis.
authors.affiliation: Department of Occupational and Environmental Health, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Guangtao
authors.initials: G
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Kaimin
authors.initials: K
authors.lastname: Rao
authors.forename: Wei
authors.initials: W
authors.lastname: Xiong
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D001564:Benzo(a)pyrene / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001564:Benzo(a)pyrene