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Long-Term Combinatorial Exposure to Trichloroethylene and Inorganic Arsenic in Genetically Heterogeneous Mice Results in Renal Tubular Damage and Cancer-Associated Molecular Changes
- Source :
- G3: Genes|Genomes|Genetics, G3: Genes, Genomes, Genetics, Vol 9, Iss 5, Pp 1729-1737 (2019)
- Publication Year :
- 2019
- Publisher :
- Genetics Society of America, 2019.
-
Abstract
- 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 (Abcb1atm1Bor, Abcb1btm1Bor) 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.
- Subjects :
- Male
trichloroethylene
Cell
environmental exposure
Kaplan-Meier Estimate
QH426-470
010501 environmental sciences
Kidney Function Tests
01 natural sciences
chemistry.chemical_compound
Mice
Renal cell carcinoma
Genetics (clinical)
renal toxicity
0303 health sciences
education.field_of_study
Kidney
Drug Synergism
Environmental exposure
Prognosis
Kidney Neoplasms
medicine.anatomical_structure
Cell Transformation, Neoplastic
Kidney Tubules
Von Hippel-Lindau Tumor Suppressor Protein
medicine.medical_specialty
Trichloroethylene
Population
Mice, Transgenic
Biology
Investigations
03 medical and health sciences
Internal medicine
Genetics
medicine
Animals
Genetic Predisposition to Disease
education
Molecular Biology
030304 developmental biology
0105 earth and related environmental sciences
arsenic
Cancer
medicine.disease
Disease Models, Animal
Endocrinology
chemistry
Mutation
Biomarkers
Toxicant
Subjects
Details
- Language :
- English
- ISSN :
- 21601836
- Volume :
- 9
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- G3: Genes|Genomes|Genetics
- Accession number :
- edsair.doi.dedup.....e4052148feb24bf327bfe87d795db790