We have explored transcriptional patterns associated with spontaneous cancer development and chemically-induced carcinogenesis. Gene expression patterns from spontaneous tumors arising in untreated B6C3F1 mouse lungs were compared with samples from lung in untreated age-matched control animals. Several canonical pathways associated with cancer were altered in the spontaneous tumors (e.g., RhoA and PTEN signaling), as well as pathways associated with metabolism (e.g., purine and pyramidine metabolism) and immune response (e.g., interleukin 8 and CXCR4 signaling). Meta-analysis of mouse tumors with human non-small lung cancer gene expression data sets were highly concordant. In another study, we also showed that exposure of B6C3F1 mice to Ginkgo biloba leaf extract involved altered transcriptional patterns associated with oncogenesis, hepatoceulluar carcinoma development and chronic xenobiotic and oxidative stress compared to spontaneous hepatocellular carcinoma. Comparing molecular pathways altered in spontaneous tumorigenesis versus those in chemically-induced tumors permitted us to explore the molecular underpinnings of these two different types of cancer progression in the context of normal subjects. In both studies, it was 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. We are currently evaluating an approach to minimize sample size in toxicogenomics experiments using order-restricted inference and mixed-directional false discovery rate criteria.

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Dunnick, June K; Merrick, B Alex; Brix, Amy et al. (2016) Molecular Changes in the Nasal Cavity after N, N-dimethyl-p-toluidine Exposure. Toxicol Pathol 44:835-47
Hayes, Schantel A; Pandiri, Arun R; Ton, Thai-vu T et al. (2016) Renal Cell Carcinomas in Vinylidene Chloride-exposed Male B6C3F1 Mice Are Characterized by Oxidative Stress and TP53 Pathway Dysregulation. Toxicol Pathol 44:71-87
Blackshear, Pamela E; Pandiri, Arun R; Nagai, Hiroaki et al. (2015) Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways. Toxicol Pathol 43:171-85
Bhusari, Sachin; Pandiri, Arun R; Nagai, Hiroaki et al. (2015) Genomic Profiling Reveals Unique Molecular Alterations in Hepatoblastomas and Adjacent Hepatocellular Carcinomas in B6C3F1 Mice. Toxicol Pathol 43:1114-26
George-Raizen, Julia B; Shockley, Keith R; Trojanowski, Nicholas F et al. (2014) Dynamically-expressed prion-like proteins form a cuticle in the pharynx of Caenorhabditis elegans. Biol Open 3:1139-49
Arnardottir, Erna S; Nikonova, Elena V; Shockley, Keith R et al. (2014) Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation. Sleep 37:1589-600
Blackshear, Pamela E; Pandiri, Arun R; Ton, Thai-Vu T et al. (2014) Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways. Toxicol Pathol 42:863-76
Hoenerhoff, Mark J; Pandiri, Arun R; Snyder, Stephanie A et al. (2013) Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicol Pathol 41:826-41
Anafi, Ron C; Pellegrino, Renata; Shockley, Keith R et al. (2013) Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues. BMC Genomics 14:362
Dunnick, June K; Brix, A; Cunny, H et al. (2012) Characterization of polybrominated diphenyl ether toxicity in Wistar Han rats and use of liver microarray data for predicting disease susceptibilities. Toxicol Pathol 40:93-106

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