Beta Androstenediol Mitigates the Damage of 1 GeV/n Fe Ion Particle Radiation to the Hematopoietic System

Abstract

Space exploration is associated with exposure to 1-3 Gy solar particle radiation and galactic cosmic radiation that could increase cancer rates. Effective nontoxic countermeasures to high linear energy transfer (LET) radiation exposure are highly desirable but currently not available. The aim was to determine whether a single subcutaneous injection of androstenediol (D 5 androsten-3b, 17b-diol [AED]) could mitigate and restore the mouse hematopoetic system from the radiation-mediated injury of 3 Gy whole-body high LET 56 Fe 26 + exposure. The findings show that postradiation AED treatment has an overall positive and significant beneficial effect to restore the levels of hematopoeitic elements ( p < 0.001). Androstenediol treatment significantly increased monocyte levels at days 4, 7, and 14 and, similarly, increased red blood cell, hemoglobin, and platelet counts. Flow cytometry analysis 14 days after radiation and AED treatment demonstrated an increase ( p < 0.05) in bone marrow cells counts. Ex vivo osteoclastogenesis studies show that AED treatment is necessary and advantageous for the development and restoration of osteoclastogenesis after radiation exposure. These findings clearly show that androstenediol functions as a countermeasure to remedy hematopoeitic injury mediated by high LET iron ion radiation. Presently, no other agent has been shown to have such properties.

Changes in the distribution and function of leukocytes after whole-body iron ion irradiation

“…In a previous study, we found 56 Fe dose-dependent decreases in blood WBCs and in all three major leukocyte types on Day 4 post-irradiation, followed by complete recovery in cell numbers by Day 113; monocyte–macrophage percentages, however, were significantly decreased in both blood and spleen [ 36 ]. Others have also noted great reduction in WBCs and the three major leukocyte types in mice during 4, 7 and 14 days after 3 Gy 56 Fe irradiation [ 47 ]. This latter study also demonstrated that subcutaneous injection of androstenediol 30 min after exposure could significantly mitigate the detrimental effect.…”