Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-l-cysteine, a metabolite of trichloroethylene

Lock, Edward A.; Barth, Jeremy L.; Argraves, Scott; Schnellmann, Rick G.

doi:10.1016/j.taap.2006.06.002

Cited by 16 publications

(16 citation statements)

References 43 publications

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“…In vitro studies with GSH conjugates of TCE show unequivocally that DCVC and its metabolites (e.g., DCVCS) are cytotoxic to primary human proximal tubular cells (Cummings & Lash, 2000; Lash, et al, 2005; Lock, et al, 2006). Similar observations were made in rodent cells (Lash, et al, 1986; Stevens, et al, 1986).…”

Section: Non-genotoxic Mechanisms Of Tce Carcinogenesismentioning

confidence: 99%

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

Rusyn

Chiu

Lash

et al. 2014

Pharmacology & Therapeutics

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The chlorinated solvent trichloroethylene (TCE) is a ubiquitous environmental pollutant. The carcinogenic hazard of TCE was the subject of a 2012 evaluation by a Working Group of the International Agency for Research on Cancer (IARC). Information on exposures, relevant data from epidemiologic studies, bioassays in experimental animals, and toxicity and mechanism of action studies was used to conclude that TCE is carcinogenic to humans (Group 1). This article summarizes the key evidence forming the scientific bases for the IARC classification. Exposure to TCE from environmental sources (including from hazardous waste sites and contaminated water) is common throughout the world. While workplace use of TCE has been declining, occupational exposures remain of concern, especially in developing countries. Strongest human evidence is from studies of occupational TCE exposure and kidney cancer. Positive, although less consistent, associations were reported for liver cancer and non-Hodgkin's lymphoma. TCE is carcinogenic at multiple sites in multiple species and strains of experimental animals. The mechanistic evidence includes extensive data on the toxicokinetics and genotoxicity of TCE and its metabolites. Together, available evidence provided a cohesive database supporting the human cancer hazard of TCE, particularly in the kidney. For other target sites of carcinogenicity, mechanistic and other data were found to be more limited. Important sources of susceptibility to TCE toxicity and carcinogenicity were also reviewed by the Working Group. In all, consideration of the multiple evidence streams presented herein informed the IARC conclusions regarding the carcinogenicity of TCE.

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Section: Non-genotoxic Mechanisms Of Tce Carcinogenesismentioning

confidence: 99%

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

Rusyn

Chiu

Lash

et al. 2014

Pharmacology & Therapeutics

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“…The cRNA preparation from 5 lg of total RNA and hybridization to Affymetrix GeneChip Porcine microarrays (catalog no. 900623) were performed at the Medical University of South Carolina (MUSC) Proteogenomics Facility (Charleston, SC) in accordance with standardized Affymetrix protocols as previously described [35][36][37]. Hybridized microarrays were scanned with a GeneChip Scanner 7G.…”

Section: Microarray Analysesmentioning

confidence: 99%

GATA Depletion Impacts Insulin-like Growth Factor 1 mRNA and Protein Levels in Luteinizing Porcine Granulosa Cells1

LaVoie

Kordus

Nguyen

et al. 2010

Biology of Reproduction

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GATA4 and GATA6 are zinc-finger transcription factors that regulate specific genes involved in steroidogenesis. Using RNA interference (RNAi)-mediated reduction of GATA4 and/or GATA6 with microarray analysis, we aimed to identify novel GATA target genes in luteinizing porcine granulosa cells under vehicle- and cAMP-treated conditions. Microarray analysis identified IGF1 mRNA to be cAMP- and GATA-responsive, and real-time PCR demonstrated that the cAMP-induced increase in IGF1 mRNA was reduced under conditions of GATA6 depletion and GATA4 plus GATA6 depletion, but not GATA4 depletion. Insulin-like growth factor 1 protein levels in media were also decreased by GATA6 or GATA4 plus GATA6 reduction. IGFBP2 and IGFBP4 mRNAs were increased and IGFBP5 mRNA decreased with vehicle and cAMP treatment under GATA4 plus GATA6 RNAi conditions. GATA6 reduction alone increased basal IGFBP4 and decreased IGFBP5 with both vehicle and cAMP, and GATA4 reduction alone lowered cAMP IGFBP5 levels with cAMP. No changes in IGFBP3 mRNA were observed with GATA reduction relative to the control RNAi condition. Levels of insulin-like growth factor binding proteins 2-5 in media as assessed by Western ligand blotting were not altered by GATA reduction. Electromobility gel shift assays with two GATA-containing oligonucleotides of the IGF1 5'-regulatory region showed GATA4 and GATA6 could bind the more proximal GATA-B site. These studies indicate that although GATA4 and GATA6 can bind the porcine IGF1 5'-region, GATA6 is functionally most important for cAMP-stimulated mRNA levels. Using microarray analysis, we identified other mRNAs that were altered by GATA-reduced conditions, including ALDH1, DIO2, and EDNRB. Our findings further support GATA as a coordinator of endocrine/paracrine/autocrine signals in the ovary.

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“…Previous studies examining changes in gene expression after exposure to TCE or a TCE metabolite have been conducted on cardiac, liver, kidney, and skin tissue (Bartosiewicz et al, 2001a;Collier et al, 2003;Chen et al, 2006;Lock et al, 2006). Studies in these organs showed minimal to no changes in gene expression, and toxic organ effects from TCE exposure.…”

Section: Discussionmentioning

confidence: 99%

“…Only the highest dose of TCE (1000 mg/kg) altered hepatic gene expression, and only three genes were mildly affected (Bartosiewicz et al, 2001a). Kidney cells exposed to S-(1,2-dichlorovinyl)-Lcysteine, a metabolite of TCE, had minor changes in gene expression (Lock et al, 2006). Exposure to TCE produced inconsistent and negligible changes in rat skin gene expression (Chen et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Modifications of proteins expressed on the oocyte plasma membrane and alterations in protein function may result from change in the expression of the genes encoding those proteins in addition to the post-translational modifications. Alteration of gene expression, or changing gene product stability or turnover mediate some toxic effects (Barker et al, 1994;Aguilar-Mahecha et al, 2001;Mizuyachi et al, 2002;Lock et al, 2006). Microarray analysis is the currently preferred technique to identify candidate genes that might be affected.…”

Section: Conflict Of Interest Statementmentioning

confidence: 99%

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Ovarian gene expression is stable after exposure to trichloroethylene

Berger

2008

Toxicology Letters

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Exposure of female rats to trichloroethylene (TCE), an environmental toxicant commonly found in ground and surface waters throughout the United States, reduces the fertilizability of oocytes produced by these females compared with oocytes from control females. Localization of cytochrome P450 2E1 and glutathione s-transferase α, TCE-metabolizing enzymes, in the ovary suggests TCE metabolism occurs in the ovary. The production of bioactive TCE metabolites in the ovary may alter female reproductive function by altering ovarian gene transcription and/or protein expression and function. The purpose of the present study was to examine ovarian gene transcription after exposure of female rats to 0.45% TCE (v/v) in 3% Tween. Control rats received 3% Tween. Microarray analysis after 1 and 5 days of exposure indicated ovarian gene transcription was maintained during TCE exposure with the possible exception of a very few genes. Although conclusions for these few genes were ambiguous from the microarray analysis due to the minimal but statistically significant reductions, quantitative real time RT-PCR (qRT-PCR) analysis indicated expression of these genes was unaltered after TCE exposure. Protein analysis confirmed qRT-PCR results. This study suggests TCE-induced reductions in oocyte fertilizability are independent of currently detectable alterations in ovarian gene expression.

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Changes in gene expression in human renal proximal tubule cells exposed to low concentrations of S-(1,2-dichlorovinyl)-l-cysteine, a metabolite of trichloroethylene

Cited by 16 publications

References 43 publications

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

Trichloroethylene: Mechanistic, epidemiologic and other supporting evidence of carcinogenic hazard

GATA Depletion Impacts Insulin-like Growth Factor 1 mRNA and Protein Levels in Luteinizing Porcine Granulosa Cells1

Ovarian gene expression is stable after exposure to trichloroethylene

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