Abstract |
5-FU is metabolized to FUTP and FdUMP in tumor cells and exhibits RNA- and DNA-directed cytotoxicity. Biochemical modulation of the intracellular metabolic pathways of 5-FU result in either selective enhancement of the antitumor effect or protection of the host. 1. Administration of pro-drugs of the active intermediates of 5-FU (FO-152, FF-705, TK-117, T-506) 2. Increase in PRPP level by inhibition of the de novo purine synthetic pathway, and greater production of cytotoxic 5-FU-containing nucleotides (MTX, MMPR) 3. Lowering of intracellular UTP pools by inhibition of de novo pyrimidine biosynthesis and enhancement of antitumor activity of 5-FU ( PALA, Acivicin) 4. Increase in the UTP level and protection against 5-FU toxicity in normal host tissue ( Uridine, Uridine + BAU, Cytidine) 5. Enhanced and prolonged inhibition of thymidylate synthetase by FdUMP ( Leucovorin, MTX) 6. Inhibition of 5-FU degradation and increase in the 5-FU tissue level ( Thymidine, Uracil)
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Authors | H Fujita |
Journal | Gan to kagaku ryoho. Cancer & chemotherapy
(Gan To Kagaku Ryoho)
Vol. 15
Issue 4 Pt 2-1
Pg. 996-1002
(Apr 1988)
ISSN: 0385-0684 [Print] Japan |
PMID | 3389839
(Publication Type: English Abstract, Journal Article)
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Chemical References |
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Topics |
- Antineoplastic Combined Chemotherapy Protocols
(pharmacokinetics, therapeutic use)
- Biotransformation
- Fluorouracil
(pharmacokinetics, therapeutic use)
- Humans
- Neoplasms
(drug therapy, metabolism)
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