Renal Cell Carcinomas in Vinylidene Chloride–exposed Male B6C3F1 Mice Are Characterized by Oxidative Stress and TP53 Pathway Dysregulation. (January 2016)

• Record Type: Journal Article
• Authors: Hayes, Schantel A.; Pandiri, Arun R.; Ton, Thai-vu T.; Hong, Hue-Hua L.; Clayton, Natasha P.; Shockley, Keith R.; Peddada, Shyamal D.; Gerrish, Kevin; Wyde, Michael; Sills, Robert C.; Hoenerhoff, Mark J.
• Is Part Of: Toxicologic pathology. Volume 44:Number 1(2016)
• Page Start: 71
• Page End: 87
• Publication Date: 2016-01
• Subjects: renal cell carcinoma -- renal tubular hyperplasia -- global gene expression -- microarray -- vinylidene chloride -- National Toxicology Program -- carcinogenicity bioassay -- quantitative PCR -- immunohistochemistry -- mutation analysis; Pathology -- Periodicals; Toxicology -- Periodicals; Pathology; Toxicology; 615.9
• DOI: 10.1177/0192623315610820
• Languages: English
• ISSNs: 0192-6233

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.