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.
Sigdestad
C P
CP
Radiation Oncology Department, University of Louisville, School of Medicine, KY 40292.
Connor
A M
AM
Sims
C S
CS
D000818:Animals; D003114:Colony-Forming Units Assay; D006410:Hematopoiesis / Q000528:radiation effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009502:Neutrons; D011833:Radiation Injuries, Experimental / Q000503:physiopathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D013154:Spleen / Q000166:cytology; D014916:Whole-Body Irradiation
D011837:Radiation-Protective Agents