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 γ-rays was examined using intestinal crypt-cell survival as an endpoint. The RBEs for 50.5 MeV neutrons relative to ¹³⁷Cs-γ-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 LD _{50 7} day (gastrointestinal syndrome), the RBE for 50.5 MeV neutrons was 1.56 and for LD _{50 30} (bone marrow syndrome), the RBE was 1.29. The ability of the phosphorothioates WR-3689 [S-2-(3-methylaminopropylamino) 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 γ-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 γ-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 LD _{50 7} were 1.12 for WR-3689 and 0.99 for WR-77913. For the bone marrow syndrome (LD _{50 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. Protective factors are higher for bone marrow than for gut. Our results differ from other investigators who have reported that some phosphorothioates protect better against fission neutrons than against X- or γ-rays.