Mechanisms of Radioprotection of Mice by Phenylhydrazine

Phenylhydrazine is a radioprotector when injected into mice 6 to 11 days before exposure to x-rays. To better define the basis for radioprotection, the following studies were made: effects of phenylhydrazine on <tex-math>${\rm LD}_{50(30)}$</tex-math>, hemopoietic regeneration in irradiated mice, hemopoiesis of unirradiated mice, hemopoietic cell radiosensitivity, and life-span of protected mice. Injection of 3.0 mg of the drug a week before irradiation increased the <tex-math>${\rm LD}_{50(30)}$</tex-math> by 140 R, which is equivalent to a dose reduction factor of about 1.2. Phenylhydrazine-treated mice survive because of hematologic recovery that becomes manifest 2 weeks after irradiation. Some of the results are consistent with the hypothesis that radioprotection by phenylhydrazine is the result of increased numbers of hemopoietic stem cells in the spleen at the time of irradiation. However, some of the colony-forming unit and splenectomy data indicate that this increase may not be the sole basis for protection, although it is clear that the spleen is involved. Protection by phenylhydrazine does not appear to be related to an increase in radioresistance of hemopoietic stem cells (colony-forming units) or to hypoxia resulting from anemia or from methemoglobin formation.