Renal Cell Carcinomas in Vinylidene Chloride Exposed Male B63FC1 Mice Are Characterized by Oxidative Stress and TP53 Overexpression

Vinylidene Chloride has been widely used in the production of plastics and flame retardants. Exposure of B6C3F1 to VDC in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increase in renal cell hyperplasias, adenomas, and carcinomas (RCCs). Global gene expression analysis showed overrepresentation of pathways associated with chronic xenobiotic and oxidative stress in RCCs from VDC-exposed B6C3F1 mice, as well as cMyc overexpression and dysregulation of Tp53 cell cycle checkpoint and DNA damage repair pathways. Trend analysis comparing RCC, VDC-exposed kidney, and vehicle 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 development of RCC in VDC-exposed mice.

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Hayes SA, Pandiri AR, Ton TV, Hong HH, Clayton NP, Shockley KR, Peddada SD, Gerrish K, Wyde M, Sills RC, Hoenerhoff MJ