Effect of pyrimidines, purines and their nucleosides on antitumor activity of 5-fluorouracil against L-1210 leukemia.

The chemotherapeutic action of 5-fluorouracil (5-FU) monotherapy on L-1210 leukemia in mice was compared with combinations of pyrimidines (uracil, uridine, deoxyuridine, cytosine, cytidine, deoxycytidine, thymine and thymidine) or purines (adenine, adenosine, deoxyadenosine, guanine, guanosine, deoxyguanosine and inosine) with 5-FU. The antitumor activity of 5-FU was enhanced by coadministration of uracil, thymine or guanosine, but the toxicity of the first two compounds was also enhanced. Only when 5-FU was administered with guanosine, was not only the antitumor activity but also the therapeutic ratio potentiated without increasing its toxicity. A time interval between the administration of 5-FU and guanosine diminished the survival effect. Therefore, the 5-FU-guanosine combination produced its optimal chemotherapeutic effect by simultaneous injection. The potentiation of antitumor effect of 5-FU by guanosine was prevented completely by cytidine or uridine, and partially by deoxyuridine, adenosine or deoxyadenosine.