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.