Depression of natural antitumor resistance of C57BL/6 mice by leukemogenic doses of radiation and restoration of resistance by transfer of bone marrow or spleen cells from normal, but not beige, syngeneic mice.

Small fractionated doses of radiation (4 weekly doses of 179 rad) induced leukemia in 93% of C57BL/6J mice. These leukemogenic doses of radiation were associated with suppression of natural killer (NK) cell activity as assessed in vitro by cytotoxic activity of spleen cells or in vivo by the ability of irradiated mice to eliminate iv inoculated radiolabeled YAC-1 lymphoma cells. This suppressive effect of irradiation was profound and prolonged, being detectable for at least 7 weeks after the last dose of radiation. NK reactivity of irradiated C57BL/6 +/+ or C57BL/6 beige mice could be reconstituted by iv transfer of 10 X 10(6) bone marrow cells or 50 x 10(6) spleen cells from normal C57BL/6 mice. In contrast, transfer of bone marrow or spleen cells from beige donors did not change the NK reactivity of irradiated C57BL/6 +/+ or C57BL/6 bg/bg recipients. It was also shown that the irradiation protocol did not eliminate potentially reactive NK cells, because following interferon incubation (10(3) U/ml), the NK activity of spleen cells of irradiated mice was substantially increased. This study supports the hypothesis of an important role for NK cells in radiation-induced leukemogenesis and forms the basis for exploration of the needed, more direct data on the effects of reconstitution of NK activity on subsequent development of tumors.