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 due to the fact that we tested for 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 toxicant vinylidene chloride (VDC) were compared to spontaneous mesotheliomas and F344/N rat mesothelial cells (Fred-PE) in order to discover the functions associated with VDC exposure. The data produced from VDC-treated animals suggested that exposure to this asbestos-related chemical is associated with the gene regulation of oncogenes, growth factors, and cell cycle response (Blackshear et al., 2015). In addition, comparisons of control and renal cell carcinoma from VDC exposed B6C3F1 mice showed overrepresentation of chronic xenobiotic and oxidative stress and dyregulation of TP53 cell cycle checkpoint and DNA damage repair pathways (Hayes et al., 2016). A separate study examined the relationship between hepatoblastoma and hepatocellular carcinoma using global gene expression analysis. The samples used in the study were obtained from HB, HCC and adjacent liver in a National Toxicology Program bioassay. There were large differences between HB and HCC samples. HB samples showed dysregulation of embryonic development, stem cell pluripotency and genomic imprinting pathways compared to HCC samples. Mouse HB was shown to be similar to human disease at the pathway level and therefore may be a good model for evaluating human cancer hazard (Bhusari et al., 2015). Another study examined the molecular consequences exposing male F344/N rats to N,N-dimethyl-p-toluidine (DMPT) on naval cavity tissue. Rat nasal 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 exposure was associated with an antioxidative damage response, cell proliferation and decreased signaling for apoptosis. The gene expression signature found here was similar to the signature found in rat nasal cavities after formaldehydge exposure, with over 1,000 shared transcriptional changes. (Dunnick et al., 2016).
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