Role of natural effector cells in the prevention of radiation-induced leukemogenesis

Four once-weekly exposures of 225 rads (R) of whole body X-irradiation causes a high incidence of lymphoma in C57BL/6 (C57) mice. The role of natural effector cells in radiation-induced leukemogenesis was investigated. Activity of natural killer (NK) and natural cytotoxic (NC) cells was depressed in irradiated mice over a prolonged period. Transplantation of bone marrow (BM) cells from normal C57 mice to irradiated mice restored their NK responses and prevented development of lymphoma. The effect of beige BM cell transfer to irradiated mice was not clear. Unlike short-term (4-hour) assay, results of long-term (20-hour) assay suggest partial restoration of NK and full restoration of NC activity in irradiated mice. Treatment of irradiated mice with polyinosinic: polycytidillic acid (poly I:C) increased NK activity and lymphoma resistance. Administration of small repeated doses of poly I:C to irradiated mice significantly prevented the development of lymphoma as well as significantly prolonging overall survival time in irradiated mice. These observations indicate that natural effector cells mediate resistance to radiation-induced leukemogenesis.