Chemical protection against gastrointestinal radiation injury in mice by WR 2822, WR 2823, or WR 109342 after 4 MeV X ray or fission neutron irradiation.
Three compounds were tested for their radioprotective properties against the effects of 4 MeV X rays or fission neutron irradiation. The endpoints tested were lethality, intestinal crypt survival, and DNA synthesizing cellularity. Two of the compounds tested; S-2(4-aminobutylamino) ethylphosphorothioic acid (WR 2822) and the aminopentylamino derivative (WR 2823) are closely related to WR 2721. The third agent was the iminothiol derivative of 1-methyl-aminoadamantine (WR 109342). All drugs were administered via intraperitoneal injections at their approximately maximum tolerated dose. WR 2822 was shown to have a slight protective effect against X rays and neutrons. The dose modification factor (DMF) for gastrointestinal death (LD50(6)) was 1.23 for X rays and 1.51 for neutrons. The assay for intestinal crypt survival produced DMF's of 1.44 (X rays) and 1.4 (neutrons). Wr 2823 also showed a protective action in these assays. The DMF for LD50(6) was 1.32 (X rays) and 1.42 (neutrons). WR 109342 was found to be extremely toxic and had no significant protective effects. All three drugs were more toxic and demonstrated less protection in most of these assays than the benchmark radioprotective agent WR 2721, although WR 2822 protected against lethal effects of fission neutrons almost as well as WR 2721. Both WR 2822 and WR 2823 produced greater protection in the crypt survival assays for fission neutron irradiation than WR 2721.
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D004247:DNA / Q000528:radiation effects; D004064:Digestive System / Q000166:cytology / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009502:Neutrons; D009680:Nuclear Fission; D009946:Organothiophosphorus Compounds / Q000494:pharmacology; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D014965:X-Rays
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; C035282:S-(2-((4-aminobutyl)amino)ethyl)phosphorothioate; C035283:WR 109342; D004247:DNA; D000218:Adamantane