Linked Life Data

2901035

Source:http://linkedlifedata.com/resource/pubmed/id/2901035

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1988-10-7
pubmed:abstractText
The mutagenicity of the glutathione S-conjugate S-(1,2-dichlorovinyl)glutathione (DCVG), the cysteine conjugates S-(1,2-dichlorovinyl)-L-cysteine (DCVC) and S-(1,2-dichlorovinyl)-DL-alpha-methylcysteine (DCVMC), and the homocysteine conjugates S-(1,2-dichlorovinyl)-L-homocysteine (DCVHC) and S-(1,2-dichlorovinyl)-DL-alpha-methylhomocysteine (DCVMHC) was investigated in Salmonella typhimurium strain TA2638 with the preincubation assay. DCVC was a strong, direct-acting mutagen; the cysteine conjugate beta-lyase inhibitor aminooxyacetic acid decreased significantly the number of revertants induced by DCVC; rat renal mitochondria (11,000 X g pellet) and cytosol (105,000 X g supernatant) with high beta-lyase activity increased DCVC mutagenicity at high DCVC concentrations. DCVG was also mutagenic without the addition of mammalian activating enzymes; the presence of low gamma-glutamyltransferase activity in bacteria, the reduction of DCVG mutagenicity by aminooxyacetic acid, and the potentiation of DCVG mutagenicity by rat kidney mitochondria and microsomes (105,000 X g pellet) with high gamma-glutamyltransferase activity indicate that gamma-glutamyltransferase and beta-lyase participate in the metabolism of DCVG to mutagenic intermediates. The homocysteine conjugate DCVHC was only weakly mutagenic in the presence of rat renal cytosol, which exhibits considerable gamma-lyase activity, this mutagenic effect was also inhibited by aminooxyacetic acid. The conjugates DCVMC and DCVMHC, which are not metabolized to reactive intermediates, were not mutagenic at concentrations up to 1 mumole/plate. The results demonstrate that gamma-glutamyltransferase and beta-lyase are the key enzymes in the biotransformation of cysteine and glutathione conjugates to reactive intermediates that interact with DNA and thereby cause mutagenicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acetylcysteine, http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Sulfur Lyases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine, http://linkedlifedata.com/resource/pubmed/chemical/Glutathione, http://linkedlifedata.com/resource/pubmed/chemical/Homocysteine, http://linkedlifedata.com/resource/pubmed/chemical/Lyases, http://linkedlifedata.com/resource/pubmed/chemical/S-(1,2-dichlorovinyl)cysteine, http://linkedlifedata.com/resource/pubmed/chemical/S-(1,2-dichlorovinyl)glutathione, http://linkedlifedata.com/resource/pubmed/chemical/S-(1,2-dichlorovinyl)homocysteine, http://linkedlifedata.com/resource/pubmed/chemical/S-1,2-dichlorovinyl-N-acetylcysteine, http://linkedlifedata.com/resource/pubmed/chemical/S-alkylcysteine lyase, http://linkedlifedata.com/resource/pubmed/chemical/gamma-Glutamyltransferase
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:volume
206
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
83-90
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Mutagenicity of amino acid and glutathione S-conjugates in the Ames test.
pubmed:affiliation
Institut für Toxikologie, Universität Würzburg, F.R.G.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't