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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
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pubmed:dateCreated |
1982-12-2
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pubmed:abstractText |
The toxicology and metabolism of 8-azaadenosine (8-azaAdo) were examined both as a single agent and in combination with the adenosine deaminase inhibitor, 2'-deoxycoformycin (dCF). The LD10 (mice) for 8-azaAdo alone on a once daily for 5 days (q.d. x 5) schedule was 30 mg . kg-1 . day-1. When the animals were pretreated with 0.1 mg . kg-1 . day-1 of dCF, the LD10 dose was reduced to 10 mg . kg-1 . day-1 x 5. The major organ toxicity seen was hepatic. Bone marrow cellularity was only slightly altered at the LD10 dose. 8-AzaAdo nucleotides were detected in the livers of treated mice as determined by high performance liquid chromatography. Further, after 2 hr of incubation, isolated rat hepatocytes accumulated 8-azaATP to levels of 2.2 mumoles/g of cells with 8-azaAdo (1 mM) alone and to 4.3 mumoles/g of cells when 8-azaAdo was used in combination with dCF (1 microgram/ml). ATP levels decreased to below the limits of detection after 2 hr in cells treated with the combination. The replacement of cellular ATP by 8-azaATP may provide an explanation for the hepatotoxicity observed in the murine toxicology studies.
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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/8-azaadenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine,
http://linkedlifedata.com/resource/pubmed/chemical/Coformycin,
http://linkedlifedata.com/resource/pubmed/chemical/Pentostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleosides
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0006-2952
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2415-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:6982043-Adenosine,
pubmed-meshheading:6982043-Animals,
pubmed-meshheading:6982043-Blood Chemical Analysis,
pubmed-meshheading:6982043-Coformycin,
pubmed-meshheading:6982043-Drug Interactions,
pubmed-meshheading:6982043-Drug-Induced Liver Injury,
pubmed-meshheading:6982043-Female,
pubmed-meshheading:6982043-Lethal Dose 50,
pubmed-meshheading:6982043-Leukocyte Count,
pubmed-meshheading:6982043-Liver,
pubmed-meshheading:6982043-Male,
pubmed-meshheading:6982043-Mice,
pubmed-meshheading:6982043-Pentostatin,
pubmed-meshheading:6982043-Rats,
pubmed-meshheading:6982043-Ribonucleosides,
pubmed-meshheading:6982043-Thymus Gland
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pubmed:year |
1982
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pubmed:articleTitle |
Biochemical pharmacology and toxicology of 8-azaadenosine alone and in combination with 2'-deoxycoformycin (pentostatin).
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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