Long-Term Combinatorial Exposure to Trichloroethylene and Inorganic Arsenic in Genetically Heterogeneous Mice Results in Renal Tubular Damage and Cancer-Associated Molecular Changes

G3: Genes, Genomes, Genetics

Rachel M. Lynch^2¹  Ivan Rusyn^3³  David W. Threadgill^4⁴  Amie Perry^1⁵ 

[1] Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843^2;Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M University, College Station, TX 77843^4;Department of Veterinary Integrative Bioscience, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843^3;Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843;Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843^1

关键词: renal toxicity;    trichloroethylene;    arsenic;    environmental exposure;   

DOI  :  10.1534/g3.119.400161

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

Trichloroethylene (TCE) and inorganic arsenic (iAs) are environmental contaminants that can target the kidney. Chronic exposure to TCE is associated with increased incidence of renal cell carcinoma, while co-exposure to TCE and iAs likely occurs in exposed human populations, such as those near Superfund sites. In order to better understand the kidney health consequences of TCE and/or iAs exposure, a genetically heterogeneous mouse population derived from FVB/NJ and CAST/EiJ mouse strains and deficient for multidrug resistance genes ( Abcb1a^tm1Bor , Abcb1b^tm1Bor ) was chronically exposed for 52-weeks to varying concentrations of TCE and iAs. Although no exposure group resulted in primary renal cell tumors, kidneys from exposed mice did have significant increases in histologic and biochemical evidence of renal tubular disease with each toxicant alone and with combined exposure, with males having significantly higher levels of damage. Although no added increase in tubular disease was observed with combination exposure compared to single toxicants, molecular changes in kidneys from mice that had the combined exposure were similar to those previous observed in an embryonic stem cell assay for the P81S TCE-induced renal cell carcinoma mutation in the Von Hippel-Lindau syndrome ( VHL ) gene. While this model more accurately reflects human exposure conditions, development of primary renal tumors observed in humans following chronic TCE exposure was not reproduced even after inclusion of genetic heterogeneity and co-carcinogenic iAs.

【 授权许可】

CC BY