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

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, adenoma, and carcinoma (RCCs). Among those differentially expressed genes between controls and RCC from 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.

The underlying molecular mechanism and potential drugs for treatment in papillary renal cell carcinoma: A study based on TCGA and Cmap datasets

“…The current study also observed that vorinostat exerts a significant influence in regulating the p53 and MAPK signaling pathway. Previous studies have indicated that both p53 and MAPK signaling pathway are clearly associated with various cellular functions, including apoptosis, cell growth, migration and induction of aging, and serve as key pathways for tumorigenesis and progression in kidney cancers ( 68 , 70 – 74 ). Therefore, vorinostat may possess an antitumor activity by inhibiting p53 and MAPK signaling pathway.…”