Schedule-dependent antitumor and toxic effects of thymidine and 5-fluorouracil in AKR and L1210 leukemias.

Abstract

The effect of thymidine (dThd) on 5-fluorouracil (FUra) toxicity to both leukemia stem cells (LCFU) and hematopoietic stem cells (NCFU) was examined. A dose of 10 mg/mouse of dThd given within 1 h before FUra enhanced FUra cytotoxicity to NCFU by a factor of about 4. This effect was also reflected in the reduction of the LD10. The dose-survival curve of FUra in AKR leukemia was modified by the prior administration of dThd 10 mg/mouse: the cytotoxic effect of FUra was enhanced by a factor of between 100 and 1000 throughout the dose range studied. These findings were reflected in the ILS studies. When given by 'high dose' infusion dThd had only a slight antitumor effect on AKR leukemia, and no effect on L1210. When large doses of dThd were infused concomitantly with FUra they potentiated its cytotoxicity against NCFU, AKR LCFU, and L1210 LCFU in a dose-dependent manner and by a maximum factor of about 70.