A systematic effort is being made by Cellular and Molecular Pathology Branch scientists in collaboration with NIEHS scientists to identify genetic alterations in oncogenes and tumor suppresser genes in the most frequent sites for spontaneous and chemical-induced neoplasms in B6C3F1 mice and NTP rat models. The goal is to increase our understanding of the significance of increased incidence of neoplasms that are found following exposure of our standard rodent models to environmental chemicals. Knowledge of the spectrum of genetic alterations that are present in chemically induced rodent tumors, their temporal appearance in the progression from preneoplastic lesions to neoplasms, and the way in which these factors may differ from tissue-to-tissue and chemical-to-chemical, will provide a molecular basis for distinguishing between spontaneous and chemically induced neoplasms. The approach is accomplished primarily from in-house collaborations. DNA and RNA are isolated from neoplasms in control and chemically treated rodents from prospective and retrospective studies and analyzed for genetic alterations using PCR based assays. Retrospective studies to identify specific genetic alterations in neoplasms from previous bioassays involve examination of archival material primarily through PCR-based assays. These studies are being designed to correlate chemical-specific properties (structural features/genotoxicity/metabolism) with characteristics of the spectrum of genetic alterations present in preneoplastic and neoplastic lesions of specific target organs. This provides an opportunity to compare classes of chemicals, to evaluate structure/activity relationships within a class, and to evaluate the response of specific target tissues to different chemicals, without having to repeat the long-term studies. More importantly the data generated from NTP studies provide a molecular understanding of cancer and its relevance to humans.

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Bhusari, Sachin; Malarkey, David E; Hong, Hue-Hua et al. (2013) Mutation Spectra of Kras and Tp53 in Urethral and Lung Neoplasms in B6C3F1 Mice Treated with 3,3',4,4'-Tetrachloroazobenzene. Toxicol Pathol :
Cesta, Mark F; Hard, Gordon C; Boyce, John T et al. (2013) Complex histopathologic response in rat kidney to oral ?-myrcene: an unusual dose-related nephrosis and low-dose alpha2u-globulin nephropathy. Toxicol Pathol 41:1068-77
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
Bolon, Brad; Garman, Robert H; Pardo, Ingrid D et al. (2013) STP Position Paper: Recommended Practices for Sampling and Processing the Nervous System (Brain, Spinal Cord, Nerve, and Eye) during Nonclinical General Toxicity Studies. Toxicol Pathol :
Koivisto, Christopher; Flake, Gordon P; Kolenda-Roberts, Holly et al. (2012) Immunohistochemical investigation of F344/N rat islet cell tumors from national toxicology program studies. Toxicol Pathol 40:751-63
Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S et al. (2012) Testing an aflatoxin B1 gene signature in rat archival tissues. Chem Res Toxicol 25:1132-44
Pandiri, Arun R; Sills, Robert C; Ziglioli, Vincent et al. (2012) Differential transcriptomic analysis of spontaneous lung tumors in B6C3F1 mice: comparison to human non-small cell lung cancer. Toxicol Pathol 40:1141-59
Kaufmann, Wolfgang; Bolon, Brad; Bradley, Alys et al. (2012) Proliferative and nonproliferative lesions of the rat and mouse central and peripheral nervous systems. Toxicol Pathol 40:87S-157S
Cullen, J M; Williams, C; Zadrozny, L et al. (2011) H-ras consensus sequence and mutations in primary hepatocellular carcinomas of lemurs and lorises. Vet Pathol 48:868-74
Hoenerhoff, Mark J; Pandiri, Arun R; Lahousse, Stephanie A et al. (2011) Global gene profiling of spontaneous hepatocellular carcinoma in B6C3F1 mice: similarities in the molecular landscape with human liver cancer. Toxicol Pathol 39:678-99

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