Power Surge: Renewed Interest in Nuclear Energy

especially in the lung and skin via inhalation and ingestion (Landolph 1994). High arsenic concentrations in drinking water (0.35–1.14 mg/L) caused increased risks of cancer of the skin, bladder, kidney, lung, and colon (National Research Council 1999). The skin cancers associated with arsenite exposure include Bowen's disease (carcinoma in situ), basal cell carcinoma, and squamous cell carci-noma (Tseng et al. 1968; Yu et al. 2006). The mouse skin model of multistage car-cinogenesis has demonstrated that cancer development results from the coordination of genetic mutation and alterations of epigenetic factors, including the machineries regulating cell proliferation and apoptosis (Hecker 1987; Zoumpourlis et al. 2003). Acquiring the capacity to evade apoptosis is a hallmark of most cancers (Hanahan and Weinberg 2000). Under normal circumstances, DNA-damaged or mutated cells are eliminated by apoptosis. Acquired resistance to apoptosis is a critical molecular event during carcinogene-sis, and disruption of apoptosis has been shown to play a major role in tumor formation and malignant progression (Hanahan and Weinberg 2000; Hickman 2002). Whereas the induction of cell proliferation by arsenite has been extensively studied, the events implicated in regulating the apoptosis of skin cells exposed to arsenite remain largely unknown. Cyclooxygenase (COX), the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids (Sheng et al. 2001; Smith et al. 1996), exists as two distinct isoforms (Feng et al. 1993). COX-2 is an inducible immediate early gene. Its expression is low or non-detectable in most tissues, but it can be readily induced in response to cell activation by cytokines, growth factors, and tumor promoters (Feng et al. 1993; Smith et al. 1996). Increasing evidence indicates that COX-2 is related to skin cancer development. Mice deficient in COX-2 develop 75% fewer tumors than their wild type littermates when subjected to a 9,10-dimethylbenz[a]anthracene/ 12-O-tetradecanoylphorbol-13-acetate two-stage chemical carcinogenesis protocol (Tiano et al. 2002). Moreover, oral administration of specific COX-2 inhibitors is effective in reducing ultraviolet-B–induced skin carcino-genesis by up to 90% (Fischer et al. 1999). Although the exact mechanisms remain to be extensively investigated, COX-2 is thought to contribute to carcinogenesis mainly by promoting cell proliferation and antagonizing cell apoptosis (Krysan et al. 2005; Tsujii and DuBois 1995; Wang et al. 2005). The role of COX-2 in apoptosis resistance and carcinogenesis suggests that COX-2 may be involved in the regulation of apoptosis of skin cells exposed to arsenite. Therefore, in the present study we examined the effect of arsenite exposure …