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Abstract
We compared in vivo radioprotective efficacy of 5-androstenediol (5-AED) to that of ten other steroids: 17α-androstenediol, dehydroepiandrosterone, 5-androstenetriol (AET), 4-androstenedione (AND), testosterone, estradiol, fluasterone, 16α-bromoepiandrosterone, 16α-fluoro-androst-5-en-17α-ol (α-fluorohydrin, AFH), and 16α-fluoro-androst-5-en-17β-ol (β-fluorohydrin). Steroids were administered 24 or 48 hr before, or 1 hr after, whole-body γ-irradiation. Two days after irradiation at 3 Gy, blood elements were counted. In addition, after irradiation at 9–12.5 Gy, survival was recorded for 30 days. The results showed radioprotective efficacy was specific for 5-AED. One other steroid, AFH, demonstrated appreciable survival effects but was less efficacious than 5-AED. AND and AET produced slight enhancement of survival in some experiments. This is the first demonstration that the prophylactic window for survival enhancement by 1 subcutaneous (sc) injection of 5-AED is as long as 48 hr in mice. Moreover, the results indicate that 1 sc injection of 5-AED 1 hr after irradiation is much less effective than 1 injection 24–48 hr before irradiation. Comparing the molecular features of steroids with radioprotective efficacy leads to the following conclusions: 1) these effects are due to interaction with specific receptors, since sc injection of extremely similar molecules with the same physicochemical properties as 5-AED were not radioprotective; 2) the17-hydroxyl group is essential; 3) this group must be in the β configuration in the absence of nearby side groups; 4) a halogen atom at 16 changes the 17-hydroxyl specificity to α; 5) the 3β-hydroxyl group is not essential; 6) addition of a 7β-hydroxyl group is deleterious; and 7) the effects are not due to activation of sex steroid receptors.