The Effect of Estradiol and Estriol on the Survival of Sublethally and Lethally Irradiated Mice

Subsequent to the studies of Treadwell et al. (1), several investigators have reported that the administration of estradiol prior to sublethal irradiation is protective (2-5). Maximum benefit is achieved if the hormone is given approximately 10 days prior to X-irradiation. With one exception (6), increased mortality has been reported when estradiol therapy follows irradiation (1-3). In an earlier report we demonstrated that, when pharmacological dosages of estradiol are administered for a 2-week period immediately after lethal irradiation, an early pattern of death occurs suggestive of primary failure of the transplanted bone marrow to establish a successful graft (7). This detrimental effect was apparent whether the donor and host were syngeneic or allogeneic. Testosterone administered during the same period did not influence the survival of the lethally irradiated and bone-marrowtransplanted recipients. Preliminary blood counts suggested that the recovery of erythroid tissues proceeded normally but that the leukocytes in the estradiol-treated mice failed to recover by the fifteenth day postirradiation, a time at which mortality was prominent in this group. The present study was designed to explore the mechanisms whereby estradiol exerted its injurious effects, to extend the observations to sublethally irradiated mice, and finally to compare these effects with that of another estrogenic hormone, estriol.