{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T05:17:56Z","timestamp":1791091076246,"version":"4.1.0"},"reference-count":80,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,11,20]],"date-time":"2008-11-20T00:00:00Z","timestamp":1227139200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2009,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Carcinogenesis is an important chronic toxicity of metals and metalloids, although their mechanisms of action are still unclear. Comparison of gene expression patterns induced by carcinogenic metals, metalloids, and model carcinogens would give an insight into understanding of their carcinogenic mechanisms. In this study, we examined the gene expression alteration in human hepatoma cell line, HepG2, after exposing to two metals (cadmium and nickel), a metalloid (arsenic), and three model carcinogenic chemicals<jats:italic>N<\/jats:italic>\u2010dimethylnitrosoamine (DMN), 12\u2010<jats:italic>O<\/jats:italic>\u2010tetradecanoylphorbol\u201013\u2010acetate (TPA), and tetrachloroethylene (TCE) using DNA microarrays with 8,795 human genes. Of the genes altered by As, Cd, and Ni exposures, 31\u201355% were overlapped with those altered by three model carcinogenic chemical exposures in our experiments. In particular, the metals and metalloid shared certain characteristics with TPA and TCE in remarkable upregulations of the genes associated with progression of cell cycle, which might play a central role in As, Cd, and Ni carcinogenesis. This characteristic of gene expression alteration was partially counteracted by intracellular accumulation of vitamin C in As\u2010exposed cells, whereas the number of cell\u2010cycle associated genes was increased in Cd\u2010 and Ni\u2010exposed cells. In our experimental conditions, ROS might have an accelerative effect on the cell proliferation mechanisms of As, but have an inhibitory effect on those of other two heavy metals. Furthermore, based on the results of Q\u2010PCR, the oncogene<jats:italic>PTTG1<\/jats:italic>, which was upregulated by all carcinogenic chemical exposures in the array experiments, might be a useful biomarker for evaluation of the carcinogenesis of inorganic carcinogens. Environ. Mol. Mutagen., 2009. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/em.20438","type":"journal-article","created":{"date-parts":[[2008,11,20]],"date-time":"2008-11-20T21:05:09Z","timestamp":1227215109000},"page":"46-59","source":"Crossref","is-referenced-by-count":39,"title":["Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal 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