Molecular Basis of Arsenic-induced Cytotoxicity, Oxidative Stress, and Genotoxicity in Human Liver Carcinoma Cells

Arsenic is a ubiquitous trace element that has been shown to induce both systemic and carcinogenic effects. Epidemiological findings indicate that arsenic is a paradoxical human carcinogen that results in increased risk of skin, lung, bladder, liver and kidney cancers. Although the systemic and carcinogenic effects of arsenic have been widely studied in a variety of systems, the mechanisms of arsenic toxicity remain largely unknown. Therefore, we proposed to use human liver carcinoma (HepG2) cells as a test model to evaluate the toxicity, oxidative stress, and genotoxic damage induced by arsenic trioxide. To achieve this goal, we performed MTT assay for cell viability, thiobarbituric acid test for lipid peroxidation, and single cell gel electrophoresis (Comet assay) for DNA damage. Data obtained from the MTT assay indicated that arsenic trioxide significantly reduced the viability of HepG2 cells, showing LD50 values of 23.2 ± 6.4 μg/mL upon 24 hours of exposure. The results of the thiobarbituric acid test showed significant increase (p<0.05) in malondialdehyde (MDA) production with increasing arsenic trioxide concentrations. Data generated from the comet assay also showed a significant increase in DNA damage, with a similar trend in comet tail-length, tail arm, and tail moment. Taken together, our results indicate that arsenic trioxide induces cytotoxic and genotoxic effects in HepG2 cells through the production of malondialdehyde (MDA), an end product of lipid peroxidation.