[In vivo distribution and activation of 5-FU--with special reference to biochemical modulation of intracellular metabolism].

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)