Induction of Cyclin D1 by Arsenite and UVB-irradiation in Human Keratinocytes

Arsenic is an environmental pollutant with carcinogenic properties that is found in many regions of the world but that poses a health risk primarily in economically disadvantaged areas. In these areas, arsenic ingestion affects various tissues, especially skin in which it acts as a comutagen with the ultraviolet component of solar radiation. Both epidemiological and experimental evidence indicates that arsenic and ultraviolet radiation act on signaling pathways that effect the expression of cyclin D1. We have previously employed an in vitro model system of human epidermal keratinocytes to study the effects of submicromolar concentrations of sodium arsenite on cyclin D1 expression. Here, we employed this system to demonstrate concordant cyclin D1-related induction profiles of ultraviolet B radiation and arsenite using cDNA microarray analysis. We also show that both of these agents act epigenetically to bring about demethylation of the cyclin D1 promoter.