Linked Life Data

7696525

Source:http://linkedlifedata.com/resource/pubmed/id/7696525

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1995-5-1
pubmed:abstractText
Tetrachloroethene causes renal tumors in male rats after inhalation exposure. Tetrachloroethene is metabolized by cytochrome P-450 and by glutathione conjugation. Cytochrome P-450-dependent oxidation results in the formation of trichloroacetyl chloride, which may acylate cellular nucleophiles; glutathione conjugation results in the formation of S-(1,2,2-trichlorovinyl)glutathione, which is metabolized to the corresponding cysteine S-conjugate. S-(1,2,2-Trichlorovinyl)-L-cysteine is activated by renal cysteine conjugate beta-lyase to give dichlorothioketene. Covalent binding of this electrophile is presumably responsible for the renal toxicity of tetrachloroethene. In this report, we demonstrate the formation of protein adducts formed from tetrachloroethene using SDS-PAGE and immunochemical detection with rabbit anti-trifluoroacetyl serum. This serum recognizes dichloroacetylated rabbit serum albumin prepared by chemical modification of rabbit serum albumin with S-ethyl dichlorothioacetate and exhibited a high specificity for N epsilon-(dichloroacetyl)-L-lysine residues in proteins as shown by competitive ELISA. In the liver of [14C]tetrachloroethene-treated rats, the antibody recognized several modified proteins in microsomes. A protein adduct in rat liver identified by GC/MS after hydrolysis was N epsilon-(trichloroacetyl)-L-lysine. Western blots of renal fractions from rats treated with [14C]tetrachloroethene (200 mg/kg) or S-(1,2,2-trichlorovinyl)-L-cysteine (40 mumol/kg, iv) suggested the presence of modified mitochondrial and cytosolic proteins; no modified proteins were detected in microsomes. Proteins of identical molecular weight were modified by tetrachloroethene and by S-(1,2,2-trichlorovinyl)-L-cysteine in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
724-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:articleTitle
Metabolism of tetrachloroethene in rats: identification of N epsilon-(dichloroacetyl)-L-lysine and N epsilon-(trichloroacetyl)-L-lysine as protein adducts.
pubmed:affiliation
Institut für Toxikologie, Universität Würzburg, FRG.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't