Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis.

摘要: Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms action are still unclear. Comparison gene expression patterns induced by carcinogenic metals, model carcinogens would give insight into understanding mechanisms. In this study, we examined the alteration in human hepatoma cell line, HepG2, after exposing to two (cadmium nickel), a metalloid (arsenic), three chemicals N-dimethylnitrosoamine (DMN), 12-O-tetradecanoylphorbol-13-acetate (TPA), tetrachloroethylene (TCE) using DNA microarrays with 8,795 genes. Of genes altered As, Cd, Ni exposures, 31–55% were overlapped those chemical exposures our experiments. particular, shared certain characteristics TPA TCE remarkable upregulations associated progression cycle, which might play central role carcinogenesis. This characteristic was partially counteracted intracellular accumulation vitamin C As-exposed cells, whereas number cell-cycle increased Cd- Ni-exposed cells. experimental conditions, ROS have accelerative effect on proliferation but inhibitory other heavy metals. Furthermore, based results Q-PCR, oncogene PTTG1, upregulated all array experiments, be useful biomarker for evaluation carcinogenesis inorganic carcinogens. Environ. Mol. Mutagen., 2009. © 2008 Wiley-Liss, Inc.