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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1993-10-15
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pubmed:abstractText |
Established cell lines derived from newborn livers of c14CoS/c14CoS and cch/cch mice were examined for differences in menadione toxicity. The 14CoS/14CoS cells exhibit 10-fold higher NAD(P)H:menadione oxidoreductase (NMO1) activity and 3-fold greater concentrations of reduced glutathione (GSH) than the ch/ch cells. In 14CoS/14CoS cells there are also 50% to 3-fold increases in glutathione transferase (GSTA1), UDP glucuronosyltransferase, and the copper, zinc-dependent superoxide dismutase activities. Catalase activity, on the other hand, is six times lower in the 14CoS/14CoS than the ch/ch line. The 14CoS/14CoS cells are two to four times more resistant to menadione killing than ch/ch cells. At concentrations of dicumarol that completely block NMO1 and GSTA1 activities, the 14CoS/14CoS cells show more than twice as much resistance to menadione toxicity than the ch/ch cells. Although superoxide formation is three times higher in untreated 14CoS/14CoS than ch/ch cells, menadione-induced superoxide formation is greater in the dying ch/ch than in the 14CoS/14CoS cells. Cellular resistance to menadione toxicity is correlated with intracellular GSH levels, rather than with the percentage of oxidized glutathione; cytotoxicity is not observed as long as GSH concentrations are sufficiently high (about 5-8 nmol/mg protein). For menadione, the results are consistent with a dominant role of GSH depletion in mediating toxicity and support a protective role for NMO1 activity. This report demonstrates the usefulness of these cell lines as a model system to study mechanisms of oxidative chemically induced toxicity, as well as to understand how intracellular levels of GSH are regulated.
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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/Dicumarol,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronosyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/NAD(P)H Dehydrogenase (Quinone),
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxides,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin K
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0041-008X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
122
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
101-7
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:7690996-Animals,
pubmed-meshheading:7690996-Cell Death,
pubmed-meshheading:7690996-Cell Line,
pubmed-meshheading:7690996-Cell Line, Transformed,
pubmed-meshheading:7690996-Dicumarol,
pubmed-meshheading:7690996-Glucuronosyltransferase,
pubmed-meshheading:7690996-Glutathione,
pubmed-meshheading:7690996-Glutathione Transferase,
pubmed-meshheading:7690996-Liver,
pubmed-meshheading:7690996-Mice,
pubmed-meshheading:7690996-NAD(P)H Dehydrogenase (Quinone),
pubmed-meshheading:7690996-Oxidation-Reduction,
pubmed-meshheading:7690996-Sulfhydryl Compounds,
pubmed-meshheading:7690996-Superoxide Dismutase,
pubmed-meshheading:7690996-Superoxides,
pubmed-meshheading:7690996-Vitamin K
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pubmed:year |
1993
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pubmed:articleTitle |
Menadione toxicity in two mouse liver established cell lines having striking genetic differences in quinone reductase activity and glutathione concentrations.
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pubmed:affiliation |
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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