The antineoplastic and biochemical effects of some 5-fluoropyrimidines.

5-fluoropyrimidine (2-HFP) were measured on Sarcoma 180 ascites cells. A marked extension of the life-span of tumor-bearing mice was afforded by i.p. injections of 5-FU, whereas both 4-HFP and 2-HFP were only weakly active. Sarcoma 180 ascites cells converted both 4-HFP and 5-FU into mono-, di-, and trinucleotide forms of 5-FU and incorporated the 5-fluoropyrimidines into RNA exclusively as 5-FU. Mice given i.p. injections of 4-HFP excreted the compound into the urine primarily as 5-FU and its metabolites. The incorporation of formate-uC into the thymine of DNA was inhibited by 5-FU, 4-HFP, and 2-HFP; measurement of the duration of inhibition by molar equivalent doses of these agents indicated that the longevity of blockade was greatest with 5-FU, while that caused by 2-HFP was the short est. Administration of an inhibitor of the activity of xanthine oxidase, 4-hydroxypyrazolo(3,4-d)pyrimidine, reduced not only the slight tumor inhibition and toxicity produced by 4-HFP, but also the conversion of this agent to 5-FU and its metabolites and the degree of inhibition of the incorporation of formate-14C into DNA, suggesting that in order to manifest biologic and biochemical activity, 4-HFP must be converted to 5-FU. The incorporation of formate-14C and hypoxanthine-8-14C into the guanine of the nucleic acids was inhibited by 5-FU, whereas the