The hematopoietic system is sensitive to
radiation injury, and mortality can occur due to blood cell deficiency and stem cell loss.
Genistein and the
angiotensin converting enzyme (
ACE) inhibitor captopril are two agents shown to protect the hematopoietic system from
radiation injury. In this study we examined the combination of
genistein with
captopril for reduction of radiation-induced mortality from hematopoietic damage and the mechanisms of radiation protection. C57BL/6J mice were exposed to 8.25Gy (60)Co total body irradiation (TBI) to evaluate the effects of
genistein and
captopril alone and in combination on survival, blood cell recovery, hematopoietic progenitor cell recovery, DNA damage, and
erythropoietin production. 8.25Gy TBI resulted in 0% survival after 30days in untreated mice. A single
subcutaneous injection of
genistein administered 24h before TBI resulted in 72% survival. Administration of
captopril in the
drinking water, from 1h through 30days postirradiation, increased survival to 55%.
Genistein plus
captopril increased survival to 95%. Enhanced survival was reflected in a reduction of radiation-induced
anemia, improved recovery of nucleated bone marrow cells, splenocytes and circulating red blood cells. The
drug combination enhanced early recovery of marrow progenitors: erythroid (CFU-E and BFU-E), and myeloid (CFU-GEMM, CFU-GM and CFU-M).
Genistein alone and
genistein plus
captopril protected hematopoietic progenitor cells from radiation-induced micronuclei, while
captopril had no effect.
Captopril alone and
genistein plus
captopril, but not
genistein alone, suppressed radiation-induced
erythropoietin production. These data suggest that
genistein and
captopril protect the hematopoietic system from
radiation injury via independent mechanisms.