Protection of survival and hematopoiesis in irradiated mice by 5-fluorouracil

Abstract

The effects of whole-body irradiation on survival and the hematopoietic system were studied in mice treated with 5-fluorouracil (5-FU). Animals (ddY-SLC male mice, 8-10 weeks old) were injected with 5-FU (i.p.) as a single dose (150 mg/kg) at various times before or after irradiation with X-rays at graded doses (4.8 to 7.6 Gy). The treatment of mice with 5-FU 5 days before irradiation was the most effective for the reduction of radiation lethality, having a radioprotective effect. The dose reduction factor (DRF) was 1.24. However, treatment with 5-FU at 1 day and 2 hours before, or at various times after irradiation significantly increased the radiation lethality compared to the untreated controls, creating a radiosensitizing effect. The decrease or the increase of radiation lethality exhibited by 5-FU was similar to the radiation-dose relationship pattern shown by endogenous and exogenous CFU-S. The pattern of change of thrombocyte counts in the circulating blood after irradiation was greatly modified by pretreatment with 5-FU 5 days before irradiation, effectively lessening the radiation-induced depression. In contrast, the post-irradiation patterns of leukocyte and erythrocyte variation did not show any significant change due to pretreatment with 5-FU.