The structural similarity of chromate to phosphate and sulfate facilitates its uptake with potential risks of cancer in humans (Costa, 1997). In vitro studies suggest Cr(VI) compounds are cytotoxic and genotoxic, and form Cr-DNA adducts (Biedermann and Landolph, 1987, Biedermann and Landolph, 1990, Patierno et al., 1988, Zhitkovich, 2005 and Zhitkovich, 2011), while others suggest that Cr(VI)-induced carcinogenicity may involve epigenetic mechanisms (Arita and Costa, 2009 and Sun et al., 2011). Although, environmental levels of CrV(VI) are thought to pose

a minimal risk due to reduction to less toxic Cr(III) by bodily fluids and cellular constituents (De Flora et al., 1997, Proctor et al., 2002 and U.S. EPA, 1991), chronic exposure to high concentrations of Cr(VI), in the form of sodium dichromate dihydrate (SDD), resulted in intestinal tumors in mice but not rats (NTP, 2008). To further investigate the key events involved in the mode of action (MOA) of intestinal Angiogenesis inhibitor tumor development, a complementary series of comparative selleck compound drinking water studies was conducted in female F344 rats and B6C3F1 mice (Kopec et al., 2012, Thompson et al., 2011a, Thompson et al., 2011b and Thompson et al., 2012). Both species exhibit similar

biochemical and histological evidence of oxidative stress, villous cytotoxicity, and crypt hyperplasia. Our mouse intestinal epithelial gene expression study reported SDD-elicited dose-dependent differential gene expression consistent with the proposed MOA (Thompson et al., 2011b), as well as identified other over-represented functions and affected pathways (Kopec et al., 2012). FAD Given the similarity of several responses in mice and rats following exposure to SDD in drinking water, comparative studies were designed to investigate species-specific effects that may explain the different tumor outcomes. More specifically, the same study design and treatment regimen (7 and 90 days) was used to obtain duodenal and jejunal epithelial tissues from SDD-treated rats for whole-genome microarray profiling. In addition to analysis for over-represented functions and phenotypically anchoring differential gene expression to gross physiology,

histopathology, and biochemical effects from complementary studies (Thompson et al., 2012), rat and mouse gene expression data were systematically compared using the same analysis methods (Kopec et al., 2012). Qualitative and quantitative differences in the number and types of differentially expressed genes were identified that not only support a proposed MOA involving oxidative stress, cytotoxicity, cell proliferation, and DNA modification but also suggest that the rat is less responsive to SDD. These differences in SDD-elicited differential gene expression may contribute to the different tumor outcomes. Detailed descriptions of the test substance, animal husbandry, and study design have been described (Thompson et al., 2011b and Thompson et al., 2012).