In vivo potentiation of 5-fluorouracil cytotoxicity against AKR leukemia by purines, pyrimidines, and their nucleosides and deoxynucleosides.

The effect of various natural pyrimidines and purines and their nucleosides and deoxynucleosides on 5-fluorouracil (FUra) cytotoxicity was examined against the transplantable AKR leukemia in female AKR mice. The spleen colony assay was used for a quantitative evaluation of the antitumor activity of the combination treatments. The base or nucleoside was administered 15 minutes before each mouse received an injection of 0.6 mg FUra. All of the compounds tested, with the exception of adenine, potentiated the cell-killing effect of FUra. On a molar basis (16-30 mumol/mouse), thymine, uracil, thymidine, and uridine enhanced FUra cytotoxicity more than a hundredfold. 2'-Deoxyuridine and the purine nucleosides and deoxynucleosides had similar potentiating activities between tenfold and fortyfold at 30 mumol per mouse. Finally, glucose, also administered 15 minutes before each mouse received an injection of 0.6 mg FUra, enhanced the antitumor activity of the drug by a factor of about five.