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Concurrent allopurinol and 5-fluorouracil: 5-fluoro-2'-deoxyuridylate formation and thymidylate synthase inhibition in rat colon carcinoma and in regenerating rat liver.
- Source :
-
Cancer chemotherapy and pharmacology [Cancer Chemother Pharmacol] 1987; Vol. 20 (3), pp. 193-7. - Publication Year :
- 1987
-
Abstract
- The formation of FdUMP and the inhibition of TS were studied in a subcutaneously growing transplantable rat colon carcinoma and in regenerating rat liver following bolus administration of 5-FU, with or without HPP pretreatment. In tumor, peak levels of FdUMP at 30 min following bolus 5-FU, 100 mg/kg, averaged 4931 +/- 587 pmol/g. Pretreatment with HPP, 50 mg/kg, 24 h and 1 h before 5-FU, reduced the peak FdUMP level to 2085 +/- 387 pmol/g. The inhibition of TS by 5-FU treatment was greater than 95% by 30 min, and after 48 h residual enzyme inhibition averaged 40%. No effect on TS inhibition by 5-FU treatment could be observed as a result of HPP pretreatment. The levels of TStot increased linearly after 5-FU treatment and doubled within 48 h. In regenerating rat liver, neither FdUMP levels nor TS inhibition, studied at 1 h after bolus 5-FU, were affected by HPP pretreatment.
- Subjects :
- Adenocarcinoma enzymology
Allopurinol pharmacology
Animals
Colonic Neoplasms enzymology
Female
Fluorodeoxyuridylate pharmacokinetics
Fluorouracil metabolism
Liver drug effects
Liver enzymology
Liver metabolism
Male
Rats
Rats, Inbred Strains
Time Factors
Adenocarcinoma metabolism
Allopurinol administration & dosage
Colonic Neoplasms metabolism
Deoxyuracil Nucleotides biosynthesis
Fluorodeoxyuridylate biosynthesis
Fluorouracil administration & dosage
Liver Regeneration drug effects
Thymidylate Synthase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0344-5704
- Volume :
- 20
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cancer chemotherapy and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 3677297
- Full Text :
- https://doi.org/10.1007/BF00570483