title: MEHP-induced oxidative DNA damage and apoptosis in HepG2 cells correlates with p53-mediated mitochondria-dependent signaling pathway.
abstract: In the present study, the effects of MEHP on human hepatocellular liver carcinoma HepG2 cells were investigated. The results showed that MEHP-induced oxidative DNA damage in the treatment groups (≥ 25.00 μM) at 24h after treatment and in the 100.00 μM treatment group at 36 h after treatment (p < 0.05 or p < 0.01). At 36 h after treatment, MEHP at higher concentrations (≥ 25.00 μM) resulted in a decrease in ATP level, and an increase in the protein levels of cytochrome c and Smac/DIABLO in the cytosol as well as the percentage of apoptotic cells. The activation of caspase-9 and -3 and the expression of the selected apoptosis-related proteins, p53, PUMA, NOXA, Bax and Bcl-2 were also induced. Furthermore, vitamin C, a scavenger of reactive oxygen species, attenuated MEHP-induced apoptosis. These findings indicated that MEHP induced oxidative DNA damage and apoptosis in HepG2 cells, and p53 and its downstream proteins were involved in mitochondria- and caspase-mediated apoptosis induced by MEHP.
authors.affiliation: Department of Occupational and Environmental Health and The MOE Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Guangtao
authors.initials: G
authors.lastname: Yang
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Zhang
authors.forename: Hongyan
authors.initials: H
authors.lastname: Zheng
authors.forename: Wenhong
authors.initials: W
authors.lastname: Lu
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives* / Q000633:toxicity; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004051:Diethylhexyl Phthalate; D053148:Caspase 3; D053453:Caspase 9; C016599:mono-(2-ethylhexyl)phthalate