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.
D000818:Animals; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005472:Fluorouracil / Q000008:administration & dosage*; D006151:Guanosine / Q000008:administration & dosage; D007939:Leukemia L1210 / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009705:Nucleosides / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage*; D011743:Pyrimidines / Q000008:administration & dosage*; D013997:Time Factors
D009705:Nucleosides; D011687:Purines; D011743:Pyrimidines; D006151:Guanosine; D005472:Fluorouracil