Protection by bone marrow grafts against lethal doses of 5-fluorouracil

C3H (H-2k) mice were treated with lethal doses of the antimetabolite 5-fluorouracil (5-FU). After 16 hr the mice received an intravenous injection of 25 X 10(6) syngeneic or allogeneic bone marrow cells. With syngeneic cells, survival after a single dose of 350 mg/kg 5-FU was increased from 27 to 83% and after 450 mg/kg 5-FU from 14 to 84%. Allogeneic CBA (H-2k) donor cells allowed 81% of the mice to survive after 350 mg/kg 5-FU and 42% after 450 mg/kg 5-FU. Allogeneic marrow from A (H-2a) donors was ineffective after both doses of 5-FU. The results show that the lethality of 5-FU is largely prevented by a hemopoietic graft. Experimentally, 5-FU belongs to the agents which may be applied in cancer chemotherapy at lethal and thus potentially tumor-eradicative doses in combination with autologous or syngeneic bone marrow. In humans it remains to be seen whether the use of this protocol is precluded by prevailing gut toxicity.