Treatment of mouse neoplasms with high doses of tubercidin.
Previous studies from this laboratory demonstrated that a potent inhibitor of nucleoside transport, nitrobenzylthioinosine (NBMPR), protected cultured cells against cytotoxic nucleosides (nebularine, tubercidin, and toyocamycin). NBMPR and its 5'-monophosphate (NBMPR-P) also protected mice against potentially lethal dosage of these agents. This report describes protection of mice from potentially lethal dosages of tubercidin by administration of NBMPR-P and the use of combinations of these agents in treatments of mice bearing transplanted neoplasms. Treatment of mice bearing i.p. implants of the Ehrlich ascites carcinoma, leukemia L1210/TG8, and colon carcinoma 26 with potentially lethal dosages of tubercidin administered together with host-protecting dosages of NBMPR-P resulted in substantial kill of neoplastic cells and long-term survivors. In these experiments, therapeutic effects were achieved at optimal dosages of NBMPR-P, which protected host vital tissues but did not protect neoplastic cells in ascitic fluids (Ehrlich ascites carcinoma cells and leukemia L1210/TG8 cells). However, at supraoptimal dosages of NBMPR-P, the occurrence of therapeutic failures which were neoplastic deaths indicated that NBMPR-P also protected the neoplastic ascites cells against tubercidin cytotoxicity. Thus, the selectivity of tubercidin toxicity toward cells of the Ehrlich ascites carcinoma and leukemia L1210/TG8 was modified by NBMPR-P dosage.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012263:Ribonucleosides / Q000008:administration & dosage*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014372:Tubercidin / Q000008:administration & dosage* / Q000633:toxicity
D012263:Ribonucleosides; D013868:Thioinosine; C001789:4-nitrobenzylthioinosine; D014372:Tubercidin