| Metabolism of daunomycin (NSC-82151) in vitro and the chemotherapeutic activity of isolated metabolites in vivo. | |
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MedLine Citation:
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PMID: 19051489 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Daunomycin (D1) was quantitatively converted to a metabolite, D2 (> 98% conversion), by an aerobic, cell-free system containing nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) and the 100,000 x g supernatant fluid of rat kidneys. Under lowered oxygen concentrations, cell homogenates plus NADPH converted D, quantitatively to an unknown metabolite, D(x), with D2 as a possible intermediate. The chromatographic properties of D(x) differed from those of D2 and the aglycones of D1 and D2 (D4 and D3 respectively). Sufficient quantities of D2 and D(x) were prepared using NADPH-supplemented cell-free preparations from the kidneys of rats to assay their chemotherapeutic activity in vivo. The metabolite D2 was as effective as daunomycin (D1) against P388 leukemic cells growing in mice, but only one sixth as active against L1210 leukemic cells growing in suspension culture. The metabolite D(x) was much less active than either D2 or D1 when assayed against L1210 cells growing in culture and was inactive against P388 cells growing in mice. |
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Authors:
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M A Asbell; E Schwartzbach; I Wodinsky; D W Yesair |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Cancer chemotherapy reports. Part 1 Volume: 56 ISSN: 0069-0112 ISO Abbreviation: Cancer Chemother Rep Publication Date: 1972 Jun |
Date Detail:
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Created Date: 2008-12-04 Completed Date: 2009-04-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7607105 Medline TA: Cancer Chemother Rep Country: United States |
Other Details:
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Languages: eng Pagination: 315-20 Citation Subset: IM |
Affiliation:
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Life Sciences Division, Arthur D. Little, Inc, Cambridge, MA, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibiotics, Antineoplastic / pharmacokinetics* Biological Assay Cell Line, Tumor Daunorubicin / pharmacokinetics* Humans Kidney / drug effects*, metabolism Mice Models, Biological NADP / metabolism Neoplasm Transplantation Oxygen / metabolism Rats Rats, Sprague-Dawley Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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PH43-65-61/PH/PHPPO CDC HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibiotics, Antineoplastic; 20830-81-3/Daunorubicin; 53-59-8/NADP; 7782-44-7/Oxygen |
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