INHIBITION OF CATABOLIC PATHWAY OF 5-FLUOROURACIL BY 3-CYANO-2,6-DIHYDROXYPYRIDINE IN HUMAN LUNG-CANCER TISSUES

Our studies of the degradation and the phosphorylation of 5-fluorouracil (5-FU) in normal and tumor lung tissues from 10 cases of lung cancer have shown that the phosphorylation of 5-FU in the tumor tissues was about 2- to 3-fold higher than that in normal tissues, and that the degradation of 5-FU in tumor tissues was nearly 6-fold higher than that in normal tissues. BOF-A2 is an anti-neoplastic agent newly synthesized from 1-ethoxymethyl-5-FU and 3-cyano-2,6-dihydroxypyridine (CNDP). The inhibitory effect of CNDP on the degradation of 5-FU in the tumor tissues was potent (IC50 3.9 x 10(-9) M). Thus, BOF-A2 exerts its anti neoplastic effect on tumors by potentiating the action of 5-FU through inhibition of 5-FU degradation by the CNDP moiety.