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The precise arsenical form(s) responsible for this carcinogenic effect are unknown, although trivalent inorganic arsenic (iAs<jats:sup>III<\/jats:sup>) and two of its toxic metabolites, monomethylarsonous acid (MMA<jats:sup>III<\/jats:sup>) and methylarsinous acid (DMA<jats:sup>III<\/jats:sup>), are attractive candidates. In an effort to better understand and compare their toxic effects in the skin, we compared the global gene expression profiles of normal human epidermal keratinocytes (NHEKs) exposed to varying noncytotoxic\/slightly cytotoxic concentrations of iAs<jats:sup>III<\/jats:sup>, MMA<jats:sup>III<\/jats:sup>, and DMA<jats:sup>III<\/jats:sup>for 24\u2009h. Exposure to each arsenical treatment group exhibited a dose effect in the number of altered genes and the magnitude of expression change in NHEKs. The most significant gene expression changes associated with iAs<jats:sup>III<\/jats:sup>and MMA<jats:sup>III<\/jats:sup>exposure were consistent with several key events believed to be important to As\u2010driven skin carcinogenesis, namely induction of oxidative stress, increased transcript levels of keratinocyte growth factors, and modulation of MAPK and NF\u2010\u03baB pathways. At both comparable arsenical concentrations and comparable NHEK toxicity, greater potential carcinogenic effects were observed in MMA<jats:sup>III<\/jats:sup>\u2010exposed NHEKs than those exposed to iAs<jats:sup>III<\/jats:sup>, including involvement of more proinflammatory signals and increased transcript levels of more growth factor genes. In contrast, none of these above\u2010mentioned transcriptional trends were among the most significantly altered functions in the DMA<jats:sup>III<\/jats:sup>treatment group. This study suggests the relative capacity of each of the tested arsenicals to drive suspected key events in As\u2010mediated skin carcinogenesis is MMA<jats:sup>III<\/jats:sup>\u2009&gt;\u2009iAs<jats:sup>III<\/jats:sup>with little contribution from DMA<jats:sup>III<\/jats:sup>. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.20677","type":"journal-article","created":{"date-parts":[[2010,9,30]],"date-time":"2010-09-30T16:11:24Z","timestamp":1285863084000},"page":"981-998","source":"Crossref","is-referenced-by-count":23,"title":["Gene expression of normal human epidermal keratinocytes modulated by trivalent arsenicals"],"prefix":"10.1002","volume":"49","author":[{"given":"Kathryn A.","family":"Bailey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan D.","family":"Hester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geremy W.","family":"Knapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell D.","family":"Owen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheau\u2010Fung","family":"Thai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,9,30]]},"reference":[{"key":"e_1_2_7_2_2","volume-title":"Monographs on the evaluation of carcinogenic risks to humans. 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