The effect of S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) was tested in the intestine for its ability to protect against fission neutron irradiation. The parameters tested were lethality, intestinal crypt survival, and DNA synthesizing cellularity. The results showed a dose modification factor (DMF) of 1.6 for lethality in mice treated with WR-2721 prior to fission neutron irradiation. This resulted in the shifting of the dose-mortality probit curve to the right by 149 rad. The crypt survival curve in protected mice was found to have a slope which was significantly different from unprotected controls. The DMF calculated at 50% crypt survival was found to be 1.3. The dose-dependent DNA synthesizing cellularity in the intestine 3 days after irradiation was tested in protected and unprotected animals. WR-2721 was shown to protect the intestine from about 120-140 rad of fission neutrons. This resulted in a DMF between 1.4 and 1.5.

The effectiveness of S-2-(3-aminopropylamino)ethylphosphorothiotic acid (WR-2721) to protect against 4 MeV X-irradiation was tested on the intestinal epithelium of the mouse. The agent was found to be most effective when injected 15 min prior to irradiation. The protective agent increased the ${\rm LD}_{50(6)}$ by 816 rads. This resulted in a dose-modification factor of 1.64. WR-2721 did not modify the inherent radiosensitivity of the intestinal crypts, but displaced the curve to the right by 758 rads. The total and per crypt cellularity in protected and unportected mice exposed to X-irradiation is described.

Intestinal crypt survival was studied in mice irradiated in air, 100% normobaric oxygen, 100% hyperbaric oxygen (30 psi), and 6% normobaric oxygen. Exposures from 900-2000 R at the rate of 47 R/min. Intestinal crypt survival was determined by the method of Hagemann, Sigdestad, and Lesher (4). The results demonstrated no difference in crypt survival for mice irradiated in air, normobaric oxygen, or hyperbaric oxygen. The crypt survival of mice was shown to have a D 0 from 377 to 380 R and a n from 7.9 to 9.7 for mice irradiated in air, 100% oxygen, or 100% oxygen at 30 psi, while mice irradiated in 6% oxygen had a <tex-math>$D_{0}=529$</tex-math> R with a n=8.1. The DMF (ratio of D 0 in 6% oxygen to D 0 in oxygen) was found to equal 1.4. The lack of difference in air and oxygen suggests the highly vascularized (oxygenated) gut is maximally sensitive. Animal lethality (<tex-math>${\rm LD}_{50(5)}$</tex-math>) is compared with crypt survival.

Intestinal crypt survival was studied using the method of Hagemann, Sigdestad and Lesher (8) in mice irradiated with 250 kVcp x-rays, cobalt-60 and fission neutrons. The D 0 's for the three treatment modalities were 377, 375 and 103 rads with extrapolation numbers of 6.2, 9.2 and 3.1, respectively. The RBE (ratio of D 0 's relative to x-rays) was 3.6 and 1.0 for neutrons and cobalt-60, respectively. The <tex-math>${\rm LD}_{50(5)}$</tex-math> values were found to be 1081 (945-1247), 1365 (1279-1456) and 252 (234-273) rads. The RBE [ratio of <tex-math>${\rm LD}_{50(5)}$</tex-math> relative to x-rays] values were found to be 4.3 and 0.8 for neutrons and cobalt-60 irradiation. Intestinal crypt survival varied from 25 to 34% of control at all of the <tex-math>${\rm LD}_{50(5)}$</tex-math> values. Total and per crypt cellularity was determined at 3 days postirradiation for each modality. The maximum proliferative response, measured at this time, occurred at or near the <tex-math>${\rm LD}_{50(5)}$</tex-math> dose for each type of radiation.