DNA microarray analysis for HepG2 cells exposed to arsenic trioxide

DNA microarray analysis revealed that the genes related to cell cycle regulation were significantly induced at non- and sub-lethal concentrations (i.e., 0.05-6 µM), while the common feature of heavy metal toxicity such as oxidative damage and following increase in glutathione, heat shock proteins, and metallothionein were confirmed at high concentrations (i.e., 6-40 µM). The concentration dependent modulation of gene expression (induction of cell cycle genes, induction of cell cycle arrest genes and apoptotic genes) following exposure to arsenic was further supported by acceleration of cell proliferation, ROS generation, and cytotoxicity. Furthermore, three cell cycle genes (i.e., CDC25B, UBE2C, and PTTG1) were proposed as marker genes of inorganic arsenic exposure. Those results indicated the potential pro-carcinogenic actions of inorganic arsenic occur in environmentally relevant exposures (as low as 0.07 µM). In this study, we examined the gene expression alteration in HepG2 cells exposed to arsenic trioxide (5 nM to 40 µM as As2O3 for 48 hours) by DNA microarray with 8795 human genes. HepG2 cells were also exposed to ε-caprolactam as a reference of non carcinogen since it is the only chemical categorized in IARC’s group 4 (Probably Not Carcinogenic). MQ water was used as control. For replicate, three dishes were prepared for each sample and individually treated in parallel.