catenin a2, gelsolin, caveolins and keratin 14這些基因是減少表現。綜之，本研究結果顯示經長時間、低劑量的處理下，無致癌性的HaCaT細胞會改變其基因表達的形式及於裸鼠身上形成腫瘤。為了更進一步了解低濃度無機砷在in vivo狀況下致癌的機制，因此先將無致癌性的人類皮膚細胞株( HaCaT ) 以皮下注射方式將細胞打入SCID mice背部。持續五個月內喝含不同濃度亞砷酸鈉的水(50, 100, 200和500 ppb)，發現若餵食含亞砷酸鈉的水會造成SCID mice身上無致癌性的HaCaT細胞轉形成腫瘤，此研究模式將有助於進一步探討無機砷致癌的分子機制。

spontaneously immortalized human skin keratinocytes (HaCaT), that were continuously exposed to non-toxic doses of arsenite (0.5 and 1 mM) for approximately 6 months. Through a continuous exposure of HaCaT to non-toxic doses of arsenite(0.5 and 1 mM) for several months, HaCaT cells became apparently tumorigenic in nude mice. In addition, we have observed the following changes caused by long term exposure to arsenite: (1) higher colony forming efficiency on soft agar; (2) higher cell density at confluency; (3) more population doublings in each passage; and (4) higher levels of GSH. By Western blotting analysis, c-fos, c-jun, keratins, catalase, heme oxygenase-1 and adhesion molecular galectin-1 were inhibited in arsenite-exposured cultures. By using a colorimetric cDNA microarray analysis, we found that the expression of dihydrodiol dehydrogenase, ferritin, thioredoxin peroxidase, oxidation resistance-1 and glutamate-cysteine ligase were enhanced in 1 mM arsenite-exposured cultures. We also found that the transmembrane protein(63kD) ,catenin a2, gelsolin, caveolins and keratin 14 were decreased in 1 mM arsenite-exposured cultures. These results suggest that after long-term and low dose exposure of HaCaT cells to arsenite leads to alterations in the expression profile and tumor formation in nude mice. We have investigated the carcinogenesis in low concentration arsenite in vivo in non-tumorigenic HaCaT cells, which were subcutaneously injected into SCID mice. Through a continuous exposure of low dose arsenite (50, 100, 200 and 500 ppb) to SCID mice for approximately 5 months, HaCaT cells became apparently tumorigenic in SCID mice. This animal model may be valuable for further investigation in molecular mechanisms of arsenic carcinogenicity.

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