ABSTRACT
Vinylidene chloride (VDC) has been widely used in the production of plastics and flame retardants. Exposure of B6C3F1 mice to VDC in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increases in renal cell hyperplasia, renal cell adenoma, and renal cell carcinomas (RCCs). Among those differentially expressed genes from controls and RCC of VDC-exposed mice, there was an overrepresentation of genes from pathways associated with chronic xenobiotic and oxidative stress as well as c-Myc overexpression and dysregulation of TP53 cell cycle checkpoint and DNA damage repair pathways in RCC. Trend analysis comparing RCC, VDC-exposed kidney, and chamber control kidney showed a conservation of pathway dysregulation in terms of overrepresentation of xenobiotic and oxidative stress, and DNA damage and cell cycle checkpoint pathways in both VDC-exposed kidney and RCC, suggesting that these mechanisms play a role in the pathogenesis of RCC in VDC-exposed mice.
Subject(s)
Carcinoma, Renal Cell , Dichloroethylenes/toxicity , Kidney Neoplasms , Oxidative Stress/drug effects , Signal Transduction/drug effects , Tumor Suppressor Protein p53/genetics , Animals , Carcinoma, Renal Cell/chemically induced , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Carcinoma, Renal Cell/physiopathology , Dose-Response Relationship, Drug , Female , Gene Expression Profiling , Kidney/drug effects , Kidney/pathology , Kidney Neoplasms/chemically induced , Kidney Neoplasms/metabolism , Kidney Neoplasms/pathology , Kidney Neoplasms/physiopathology , Male , Mice , Mutation , Toxicity Tests, Chronic , Tumor Suppressor Protein p53/metabolismABSTRACT
The 2014 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri" was held in Washington, D.C., in advance of the Society of Toxicologic Pathology's 33rd annual meeting. The goal of this annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for audience voting and discussion. Some lesions and topics covered during the symposium included a pulmonary mucinous adenocarcinoma in a male B6C3F1 mouse; plexiform vasculopathy in Wistar Han (Crl:WI[Han]) rats; staging of the estrous cycle in rats and mice; peri-islet fibrosis, hemorrhage, lobular atrophy and inflammation in male Sprague-Dawley (SD) rats; retinal dysplasia in Crl:WI[Han] rats and B6C3F1 mice; multicentric lymphoma with intravascular microemboli and tumor lysis syndrome, and 2 cases of myopathy and vascular anomaly in Tg.rasH2 mice; benign thymomas in Crl:WI[Han] rats; angiomatous lesions in the mesenteric lymph nodes of Crl:WI[Han] rats; an unusual foveal lesion in a cynomolgous monkey; and finally a series of nomenclatures challenges from the endocrine International Harmonization of Nomenclature and Diagnostic Criteria (INHAND) Organ Working Group (OWG).
