Subcutaneous administration of genistein prior to lethal irradiation supports multilineage, hematopoietic progenitor cell recovery and survival.

ABSTRACT

PURPOSE: Genistein, a non-toxic isoflavone from soybeans, has immunomodulating and radioprotective properties. In this study we investigated the mechanism for genistein-induced radioprotection by evaluating the recovery of bone marrow cells and peripheral blood hematology in lethally irradiated mice. MATERIALS AND METHODS: CD2F1 male mice received a single subcutaneous injection of genistein (200 mg/kg) 24 h prior to a lethal, total body irradiation dose (8.75 Gy) of cobalt-60 gamma radiation. Survival and hematopoietic reconstitution were evaluated over nine weeks post-irradiation. Hematopoietic progenitor colony-forming cell assays were used to assess the reconstitution of bone marrow after radiation-induced myelosuppression. RESULTS: A total of 97% of genistein-treated mice survived after 30 days while 31% of vehicle-treated and 0% of untreated mice survived. The improvement in survival was related to accelerated neutrophil and platelet recovery, resulting from earlier and more pronounced multilineage, hematopoietic progenitor cell reconstitution in the femoral marrow compartment. Myeloid and erythroid progenitor cell numbers at day 15 post-irradiation were 6-fold to 20-fold higher in genistein-treated animals than in control animals. CONCLUSIONS: These results demonstrate that a single subcutaneous administration of genistein 24 h before irradiation provides significant radioprotection to the hematopoietic progenitor cell compartment.