Document Detail


Inhibition by oxonic acid of gastrointestinal toxicity of 5-fluorouracil without loss of its antitumor activity in rats.
MedLine Citation:
PMID:  7689420     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The possibility of decreasing the gastrointestinal (GI) toxic effects of 5-fluorouracil (5-FU) on the digestive tract such as its injury of cells and induction of diarrhea, without reducing its antitumor activity, was investigated in rats. Oxonic acid was found to inhibit the phosphorylation of 5-FU to 5-fluorouridine-5'-monophosphate catalyzed by pyrimidine phosphoribosyl-transferase in a different manner from allopurinol in cell-free extracts and intact cells in vitro. On p.o. administration of 5-FU (2 mg/kg) and a potent inhibitor of 5-FU degradation to Yoshida sarcoma-bearing rats, oxonic acid (10 mg/kg) was found to inhibit the formation of 5-fluorouridine-5'-monophosphate from 5-FU and its subsequent incorporation into the RNA fractions of small and large intestine but not of tumor and bone marrow tissues. This selective inhibition of 5-FU phosphorylation in the GI tract was due to the much higher concentrations of oxonic acid in GI tissues than in other tissues and the blood. On p.o. administration with the 5-FU derivative, UFT, which is a combined form of 1 M tegafur and 4 M uracil and usually administered p.o. to cancer patients in Japan, oxonic acid (10-50 mg/kg) markedly reduced injury of GI tissues and/or severe diarrhea without influencing the antitumor effect of UFT. These findings suggest that coadministration of oxonic acid suppresses the GI toxicity of 5-FU and its derivatives without affecting their antitumor activity and thus prolongs the life span of cancer-bearing rats.
Authors:
T Shirasaka; Y Shimamoto; M Fukushima
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cancer research     Volume:  53     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-09-24     Completed Date:  1993-09-24     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4004-9     Citation Subset:  IM    
Affiliation:
Institute for Pathogenic Biochemistry in Medicine, Taiho Pharmaceutical Co., Ltd., Saitama, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Digestive System / drug effects*,  metabolism
Fluorouracil / administration & dosage,  adverse effects,  antagonists & inhibitors*,  metabolism
Infusions, Intravenous
Liver / metabolism
Male
Oxonic Acid / administration & dosage,  metabolism,  pharmacology*
Phosphorylation / drug effects
RNA / metabolism
Rats
Sarcoma, Yoshida / drug therapy,  metabolism
Uracil Nucleotides / metabolism
Chemical
Reg. No./Substance:
0/Uracil Nucleotides; 51-21-8/Fluorouracil; 63231-63-0/RNA; 796-66-7/5-fluorouridine 5'-phosphate; 937-13-3/Oxonic Acid

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


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