Mehp-Induced Oxidative DNA Damage and Apoptosis in Hepg2 Cells Correlates with P53-Mediated Mitochondria-Dependent Signaling Pathway

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  • 作者：Yang, G., Zhou, X., Wang, J., Zhang, W., Zheng, H., Lu, W. & Yuan, J.
  • 期刊：Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 50, 2424-2431 (2012)
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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.

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