Modification of neutron-induced hematopoietic effects by chemical radioprotectors.

Nine drugs, WR-347, WR-1065, WR-2529, WR-2721, WR-3689, WR-44923, WR-151327, WR-109342, and WR-168643, were assayed for intraperitoneal pharmacological toxicity, hematopoietic lethality, and spleen stem cell survival in C57/Bl mice in conjunction with whole-body fission neutron irradiation. In addition, WR-3689, WR-109342, and WR-168643 were used with per os administration to determine hematopoietic lethality. Drug toxicities after intraperitoneal administration, as determined by LD50's, ranged from 37 mg/Kg for WR-109342 to 2901 mg/Kg for WR-2529. Following oral administration drug toxicities ranged from 58 mg/Kg (WR-109342) to 1816 mg/Kg (WR-3689). Dose modification factors as determined by LD50(30)'s following intraperitoneal administration ranged from 1.08 for WR-347 to 1.49 for WR-2529. Of the drugs orally administered, WR-168643 was the best protector with a DMF of 1.51. Spleen stem cell survival, which was performed only after intraperitoneal drug administration, provided no significant differences in dose modification factors.