Linked Life Data

8923030

Source:http://linkedlifedata.com/resource/pubmed/id/8923030

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
139
pubmed:dateCreated
1997-2-20
pubmed:abstractText
A number of xenobiotics, including the synthetic antioxidant ethoxyquin, inhibit aflatoxin B1 (AFB1)-induced hepatocarcinogenesis in the rat. Two detoxification enzymes that mediate ethoxyquin-induced chemoprotection against AFB1 have been identified by protein purification: a glutathione S-transferase (GST) Yc2 subunit with at least 100-fold greater activity towards AFB1-8,9-epoxide than previously studied transferases, and a unique aldehyde reductase with activity towards the dialdehydic form of AFB1-8,9-dihydrodiol. Molecular cloning has revealed that the Yc2 subunit is a class alpha GST and that the aflatoxin-metabolizing aldehyde reductase (AFAR) is a distant member of the aldo-keto reductase superfamily. Enzyme assay and western blotting have shown that many chemoprotectors, such as ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, oltipraz and indole-3-carbinol, that inhibit AFB1-mediated hepatocarcinogenesis induce both GST Yc2 and AFAR. However, western blotting suggests that these enzymes are not always coordinately regulated, as treatment with phenobarbital and beta-naphthoflavone results in differences in the relative increase in hepatic GST Yc2 and AFAR. These findings indicate that GST Yc2 and AFAR represent important resistance mechanisms against AFB1 in the rat. This conclusion is supported by the observation that GST Yc2 and AFAR are overexpressed in rat liver preneoplastic nodules, which display pleiotropic drug resistance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-5038
pubmed:author
pubmed:issnType
Print
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-87
pubmed:dateRevised
2005-11-16
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Regulation of glutathione S-transferases and aldehyde reductase by chemoprotectors: studies of mechanisms responsible for inducible resistance to aflatoxin B1.
pubmed:affiliation
Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, UK.
pubmed:publicationType
Journal Article, Review