We have explored transcriptional patterns associated with spontaneous cancer development and chemically-induced carcinogenesis. In these studies, it is necessary to control mixed directional false discovery rate since we typically perform multiple comparisons and there is a potential for directional errors when declaring genes to be up- or downregulated. Global gene expression patterns of tumors arising in response to the Tetrabromobisphenol A (TBBPA), a widely used flame retardant. TBBPA showed evidence of uterine tumors in female Wistar-Han rats in a two-year study. Female Wistar-Hans rats were exposed to 0, 25, 250 or 1000 mg/kg/day by oral gavage for 13 weeks. Transcriptional analyses revealed that TBBPA-induced changes occurred in the liver and were associated with interferon and metabolic networks, but induced few changes in the uterus. Another study examined the molecular consequences exposing male F344/N rats to N,N-dimethyl-p-toluidine (DMPT) and p-toluidine in liver. Rat liver tumors were previously found to occur in a two-year cancer study of female and male F344/N rats exposed to DMPT. In this study, rats were exposed to DMPT (0, 1, 6, 20, 60 and 120 mg/kg) by oral gavage for 5 days. Gene expression patterns were compared between 0 and 120 mg/kg and revealed that DMPT and p-toluidine exposure was associated with an antioxidative damage response (activation of the Nrf2 pathways) and hepatic toxicity. Benchmark dose (BMD) calculations yielded lower confidence bound benchmark doses of 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine.
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