This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Arsenic is an environmental toxicant and carcinogen of global public health concern and long-term exposure to arsenic principally through drinking water is correlated with increased risk to skin cancer. We propose to investigate the time course alteration in genome-wide expression profiles of keratinocyte cell line to chronic exposure concentrations of arsenic trioxide. We hypothesize that in chronically exposed arsenic trioxide treated cells over a time course of two weeks, mimicking keratinocyte differentiation, toxic insult by arsenic trioxide will cause alterations in gene expression leading to carcinogenesis. RNA was extracted from untreated HaCaT and HaCaT cell chronically exposed to arsenic trioxide passage 22. The microarray gene expression data reveals 14 up-regulated genes and 21 down-regulated genes. Long-term cultures of HaCaT on collagen IV show that acute exposure at Day 2 and Day 5 is comparable at 1ppm. As incubation time increases viability decreases with increasing dose. We demonstrated through MTT and Comet assay that arsenic is cytotoxic and genotoxic to HaCaT cell. In the next year, additional microarrays datasets will be generated combined with assays to determine the biological pathways altered by chronic exposure of HaCaT cell to arsenic trioxide during the time course of 14 days.
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