Source:http://linkedlifedata.com/resource/pubmed/id/12557262
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2003-1-30
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pubmed:abstractText |
We have shown previously that the alpha class murine glutathione transferase (GST) isoenzyme mGSTA1-1, unlike other mammalian class alpha GSTs, is highly efficient in catalyzing the glutathione (GSH) conjugation of (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE], which is the ultimate carcinogenic metabolite of benzo[a]pyrene. The present studies were undertaken to determine the efficacy of mGSTA1-1 in cellular protection against (+)-anti-BPDE-induced DNA damage in HepG2 cells stably transfected with mGSTA1 cDNA. Untransfected HepG2 cells, vector-transfected HepG2 cells (HepG2-vector), and cells transfected with mGSTA4 cDNA (HepG2-mGSTA4), an alpha class murine GST isoenzyme with low (+)-anti-BPDE-GSH conjugating activity, were used as controls for comparison. Intracellular GSH conjugation of (+)-anti-BPDE was significantly higher in mGSTA1-1-overexpressing HepG2 cells (HepG2-mGSTA1) than in HepG2-vector or HepG2-mGSTA4 cells. The formation of DNA-adducts of (+)-anti-BPDE, following a 10-, 20-, or 30-min exposure to 0.1, 0.5, or 1.0 microM [3H](+)-anti-BPDE, was reduced significantly in cells transfected with mGSTA1-1 compared with HepG2-vector or untransfected HepG2 cells. Consistent with the results with purified protein, overexpression of mGSTA4-4 had no effect on (+)-anti-BPDE-induced DNA damage. The results of the present study indicated that mGSTA1-1 was exceptionally effective in affording protection against (+)-anti-BPDE-induced DNA damage in a cellular system.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrenes,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Adducts,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/glutathione S-transferase alpha
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0899-1987
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 2003 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:volume |
36
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
67-73
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:12557262-Animals,
pubmed-meshheading:12557262-Benzopyrenes,
pubmed-meshheading:12557262-Blotting, Western,
pubmed-meshheading:12557262-DNA Adducts,
pubmed-meshheading:12557262-DNA Damage,
pubmed-meshheading:12557262-DNA Repair,
pubmed-meshheading:12557262-Glutathione Transferase,
pubmed-meshheading:12557262-Humans,
pubmed-meshheading:12557262-Isoenzymes,
pubmed-meshheading:12557262-Mice,
pubmed-meshheading:12557262-Transfection,
pubmed-meshheading:12557262-Tumor Cells, Cultured
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pubmed:year |
2003
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pubmed:articleTitle |
Exceptional activity of murine glutathione transferase A1-1 against (7R,8S)-dihydroxy-(9S,10R)-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene-induced DNA damage in stably transfected cells.
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pubmed:affiliation |
Department of Pharmacology and University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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