Document Detail


Metabolism of daunomycin (NSC-82151) in vitro and the chemotherapeutic activity of isolated metabolites in vivo.
MedLine Citation:
PMID:  19051489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
M A Asbell; E Schwartzbach; I Wodinsky; D W Yesair
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cancer chemotherapy reports. Part 1     Volume:  56     ISSN:  0069-0112     ISO Abbreviation:  Cancer Chemother Rep     Publication Date:  1972 Jun 
Date Detail:
Created Date:  2008-12-04     Completed Date:  2009-04-24     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7607105     Medline TA:  Cancer Chemother Rep     Country:  United States    
Other Details:
Languages:  eng     Pagination:  315-20     Citation Subset:  IM    
Affiliation:
Life Sciences Division, Arthur D. Little, Inc, Cambridge, MA, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
PH43-65-61/PH/PHPPO CDC HHS
Chemical
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 20830-81-3/Daunorubicin; 53-59-8/NADP; 7782-44-7/Oxygen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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