Trichloroethylene metabolism in vitro: an EPR/SPIN trapping study

Steel-Goodwin, Linda; Pravecek, Tasha L.; Carmichael, Alasdair J.

doi:10.1177/096032719601501103

Cited by 10 publications

(2 citation statements)

References 14 publications

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“…Free radicals have also been trapped when TCE is incubated with liver slices in vitro (38). Consequently, there is the possibility that radicals may contribute to the carcinogenic response.…”

Section: Evidence Ofsomatic Mutationmentioning

confidence: 99%

Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate.

Bull

2000

Environ Health Perspect

127

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Trichloroethylene (TCE) induces liver cancer in mice but not in rats. Three metabolites of TCE may contribute-chloral hydrate (CH), dichloroacetate (DCA), and trichloroacetate (TCA). CH and TCA appear capable of only inducing liver tumors in mice, but DCA is active in rats as well. The concentrations of TCA in blood required to induce liver cancer approach the mM range. Concentrations of DCA in blood associated with carcinogenesis are in the sub-pM range. The carcinogenic activity of CH is largely dependent on its conversion to TCA and/or DCA. TCA is a peroxisome proliferator in the same dose range that induces liver cancer. Mice with targeted disruptions of the peroxisome proliferator-activated receptor alpha (PPARa) are insensitive to the liver cancer-inducing properties of other peroxisome proliferators. Human cells do not display the responses associated with PPARa that are observed in rodents. This may be attributed to lower levels of expressed PPARax in human liver. DCA treatment produces liver tumors with a different phenotype than TCA. Its tumorigenic effects are closely associated with differential effects on cell replication rates in tumors, normal hepatocytes, and suppression of apoptosis. Growth of DCA-induced tumors has been shown to arrest after cessation of treatment. The DCA and TCA adequately account for the hepatocarcinogenic responses to TCE. Low-level exposure to TCE is not likely to induce liver cancer in humans. Higher exposures to TCE could affect sensitive populations. Sensitivity could be based on different metabolic capacities for TCE or its metabolites or result from certain chronic diseases that have a genetic basis. Key words: chloral hydrate, dichloroacetate, liver tumors, mode of action, trichloroacetate, trichloroethylene. -Environ Health Perspect 108(suppl 2):241-259 (2000). http.//ehpnetl.niehs.nih.gov/docs/2000/suppl-2/24 1-259bull/abstract. html

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Section: Evidence Ofsomatic Mutationmentioning

confidence: 99%

Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate.

Bull

2000

Environ Health Perspect

127

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“…If the formation of these metabolites can be attenuated, tumor formation can be inhibited. Several P450s have been implicated in TCE bio-activation, including CYP2E1 and CYP1A2 in man and lab animals [4,10,11]. In animal studies, the administration of TCE produced liver toxicity in the rat and its toxicity may be potentiated by alcohol consumption [12].…”

Section: Introductionmentioning

confidence: 99%

Abri Cantongnesis Modulates Detoxifying Enzymes to Ameliorate Hepatotoxicity in Rats

Song¹

2014

Altern Integ Med

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Abri cantongnesis in combination with herbs are used for treatment of diseases. However, the detail of its pharmacological activities is lacking. In this study, the chemoprotective effects of the active fraction of Abri cantongnesis on toxicant-induced liver toxicity in rats were studied. The Abri cantongnesis extract was orally administered to SD rats for three days before treatment of rats with trichloroethylene once for two days. Rat urines and hepatic enzymes were collected for analysis. The results showed that CYP 1A and CYP 2E1 and glutathione transferase increased over 45% while the activity of diaphorase increased by 30%. These enzyme activities were increased with the extract concentration. However, only UGT showed a decrease in activity upon treatment with Abri cantongnesis. The treatment of rats with Abri cantongnesis caused an increase in catalytic activities of CYP 1A and CYP 2E1, GST and diaphorase in the rat. The results show that Abri cantongnesis enhanced elimination of trichloroethylene and its metabolites; thus the treatment of Abri cantongnesis can reduce liver toxicity in rats. The findings suggest that Abri cantongnesis has chemopreventive effects on toxicants-induced hepatotoxicity in rats. The Abri cantongnesis can be used as a chemo-protective agent for the liver.

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Multiscale Integration of Toxicokinetic and Toxicodynamic Processes: From Cell and Tissue to Organ and “Whole Body” Models

Georgopoulos¹,

Isukapalli²,

Androulakis³

et al. 2009

General, Applied and Systems Toxicology

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This chapter presents a systematic summary overview of coordinated efforts taking place at the environmental bioinformatics and Computational Toxicology Center ( ebCTC.org ) towards developing a mechanistic modeling framework that integrates multiple scales of coupled toxicokinetic and toxicodynamic processes. This framework employs highly modular “whole body” computational descriptions of the human and of selected model organisms that incorporate a hierarchy of alternative formulations representing biological events in “virtual” tissues and organs. This approach allows the mechanistic consideration of multiple scales of interlinked phenomena that include molecular interactions; dynamics of intracellular biomolecular networks; spatial and stochastic aspects of cell biochemistry; integrative coupling of cellular‐level processes related to common endpoints; extracellular signaling and cell‐cell communication and interaction; aspects of functional heterogeneity in multicellular structures; dynamics of histomorphological and histopathological processes at the tissue level; and integrative coupling of processes across scales, resulting in different physiosystem phenotypes for health and disease states. The ebCTC framework offers a range of combined approaches for coupling processes and “transferring and integrating” information across multiple strata of biological organization, ranging from formal methods of multiscale analysis, including statistical descriptions of multicellular kinetics and dynamics, to simplified “top‐down” approaches, incorporating both mechanistic and phenomenological formulations that rely on point and distributional parameterizations of the finer scales. The computational implementation of the framework employs a combination of agent‐, network‐, and field‐based modeling methods. Example applications of various components of this framework are presented, spanning the range from molecular interactions to bionetwork and cellular dynamics to multiscale problems at the tissue and organ levels.

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Trichloroethylene metabolism in vitro: an EPR/SPIN trapping study

Cited by 10 publications

References 14 publications

Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate.

Mode of action of liver tumor induction by trichloroethylene and its metabolites, trichloroacetate and dichloroacetate.

Abri Cantongnesis Modulates Detoxifying Enzymes to Ameliorate Hepatotoxicity in Rats

Multiscale Integration of Toxicokinetic and Toxicodynamic Processes: From Cell and Tissue to Organ and “Whole Body” Models

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