title: 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, 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.
authors.affiliation: Charles River Laboratories, Pathology Associates, Research Triangle Park, North Carolina, USA.
authors.forename: Schantel A
authors.initials: SA
authors.lastname: Hayes
authors.affiliation: Experimental Pathology Laboratories Inc., Research Triangle Park, North Carolina, USA Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Arun R
authors.initials: AR
authors.lastname: Pandiri
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Thai-vu T
authors.initials: TV
authors.lastname: Ton
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Hue-Hua L
authors.initials: HH
authors.lastname: Hong
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Natasha P
authors.initials: NP
authors.lastname: Clayton
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Keith R
authors.initials: KR
authors.lastname: Shockley
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.affiliation: Microarray Core, Toxicology and Pharmacology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Gerrish
authors.affiliation: Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wyde
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Sills
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicologic Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA hoenerho@med.umich.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoenerhoff
mesh_terms: D000818:Animals; D002292:Carcinoma, Renal Cell / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004000:Dichloroethylenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D036401:Toxicity Tests, Chronic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D004000:Dichloroethylenes; D016159:Tumor Suppressor Protein p53; C029297:vinylidene chloride
keywords: National Toxicology Program; carcinogenicity bioassay; global gene expression; immunohistochemistry; microarray; mutation analysis; quantitative PCR; renal cell carcinoma; renal tubular hyperplasia; vinylidene chloride