Response of mouse tissues to neutron and gamma radiation: protection by WR-3689 and WR-77913.
The response of mouse intestine to d(22 MeV) + Be neutrons, p(50.5 MeV) + Be neutrons, or 137Cs gamma-rays was examined using intestinal crypt-cell survival as an endpoint. The RBEs for 50.5 MeV neutrons relative to 137Cs-gamma-rays of response levels of 5 and 50 surviving cells/circumference were 1.80 and 1.86. For d(22 MeV) + Be neutrons, the RBEs at comparable cell survivals were 1.86 and 1.93. For LD50/7 day (gastrointestinal syndrome), the RBE for 50.5 MeV neutrons was 1.56 and for LD50/30 (bone marrow syndrome), the RBE was 1.29. The ability of the phosphorothioates WR-3689 [S-2-(3-methylamino-propylamino) ethylphosphorothioic acid, 450 mg/kg] and WR-77913 [S-2-(3-amino-2-hydroxypropyl) phosphorothioic acid, 800 mg/kg] to protect against p(50.5 MeV) + Be neutrons and gamma-rays also was examined in mice using lethality at seven or 30 days as the endpoints. Results were compared to previous studies with d(22 MeV) + Be neutrons WR-2721 (400 mg/kg), an appropriate comparison given the similar RBEs of the two neutron sources relative to gamma-rays. WR-77913 is a less effective protector than is WR-2721 while in some cases WR-3689 is as effective as WR-2721. The neutron DMFs for LD50/7 were 1.12 for WR-3689 and 0.99 for WR-77913. For the bone marrow syndrome (LD50/30) the neutron DMFs were 1.47 for WR-3689 and 1.21 for WR-77913. For a given type of radiation, WR-3689 is more effective than WR-77913. Both phosphorothioates protect less well against neutron radiation than against photons, as was reported previously for WR-2721.(ABSTRACT TRUNCATED AT 250 WORDS)
Rasey
J S
JS
Department of Radiation Oncology, University of Washington, Seattle 98195.
Magee
S
S
Nelson
N
N
Chin
L
L
Krohn
K A
KA
D004999:Amifostine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D007422:Intestines / Q000528:radiation effects; D051379:Mice; D009502:Neutrons; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000473:pathology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*
D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; C049344:S-2-(3-methylaminopropylamino)ethylphosphorothioic acid; C035284:WR 77913; D004999:Amifostine