Document Detail


Dose-dependent binding of trichloroethylene to hepatic DNA and protein at low doses in mice.
MedLine Citation:
PMID:  9366897     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Trichloroethylene (TCE) is a widely used industrial chemical and a low level contaminant of surface and ground water in industrialized areas. It is weakly mutagenic in several test systems and carcinogenic in rodents. However, the mechanism for its carcinogenicity is not known. We investigated the binding of [1,2-14C]TCE ([14C]TCE) to liver DNA and proteins in male B6C3F1 mice at doses more relevant to humans than used previously. The time course for the binding was studied in animals dosed with 4.1 micrograms [14C]TCE/kg body weight (b.w.) and sacrificed between 0.5 and 120 h after i.p. injection. A dose response study was carried out in mice given [14C]TCE at doses between 2 micrograms/kg and 200 mg/kg b.w. and sacrificed 2 h post-treatment. [14C]TCE associated with the DNA and protein extracts was measured using accelerator mass spectrometry. The highest level of protein binding (2.4 ng/g protein) was observed 1 h after the treatment followed by a rapid decline, indicating pronounced instability of the adducts and/or rapid turnover of liver proteins. DNA binding was biphasic with the first peak (75 pg/g DNA) at 4 h. However, the highest binding (120 pg/g DNA) was found between 24 and 72 h after the treatment. Dose response curves were linear for both protein and DNA binding. The binding of TCE metabolites to DNA was ca. 100-fold lower than to proteins when calculated per unit weight of macromolecules and when measured 2 h post-exposure. This study shows that TCE metabolites bind to DNA and proteins in a dose-dependent manner in liver, one of the target organs for its tumorigenicity. Thus, protein and DNA adduct formation should be considered as a factor in the tumorigenesis of TCE.
Authors:
A Kautiainen; J S Vogel; K W Turteltaub
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Chemico-biological interactions     Volume:  106     ISSN:  0009-2797     ISO Abbreviation:  Chem. Biol. Interact.     Publication Date:  1997 Sep 
Date Detail:
Created Date:  1997-12-08     Completed Date:  1997-12-08     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0227276     Medline TA:  Chem Biol Interact     Country:  IRELAND    
Other Details:
Languages:  eng     Pagination:  109-21     Citation Subset:  IM    
Affiliation:
Biology and Biotechnology Research Program, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carbon Radioisotopes / metabolism
Carcinogens / metabolism*,  toxicity
Chromatography, High Pressure Liquid
DNA / metabolism*
DNA Adducts / metabolism
Dose-Response Relationship, Drug
Liver / drug effects*
Male
Mass Spectrometry
Mice
Mice, Inbred Strains
Nucleotides / metabolism
Protein Binding
Proteins / metabolism*
Time Factors
Trichloroethylene / metabolism*,  toxicity
Grant Support
ID/Acronym/Agency:
ESO-04705/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Carbon Radioisotopes; 0/Carcinogens; 0/DNA Adducts; 0/Nucleotides; 0/Proteins; 79-01-6/Trichloroethylene; 9007-49-2/DNA

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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