Comparative intestinal and testes toxicity of four aminothiols in irradiated and nonirradiated mice

Intestinal and testicular toxicity in groups of nonirradiated and irradiated mice were investigated after intraperitoneal injection of aminothiol compounds or saline. Four aminothiols were studied. Three were prodrugs: WR-2721, WR-3689, and WR-151327 and one was the active form of WR-2721: WR-1065. Thirty minutes after injection, the mice were sham-irradiated or bilaterally exposed (whole body) to 60Co gamma-irradiation at a dose rate of 1 Gy per min to a total dose of 15 Gy. Four days after injection, mice were euthanised, and the intestines and testes were removed and histologically examined. The intestinal crypt cell number was increased in all the irradiated mice given WR-compounds compared to controls (P < 0.05). Interestingly, the crypt cell number in nonirradiated mice given WR-1065 was also greater than control or WR-2721 (P < 0.05) treated mice. Germinal cell numbers from testes of mice administered aminothiols prior to radiation decreased or did not change. Some swelling of the seminiferous tubules was also observed. The germinal cell numbers in sham-irradiated mice were also less than the controls. Thus, aminothiol addition can provide limited protection to intestinal crypt cells but not to germinal cells of the testes in response to gamma-irradiation. There is also evidence that aminothiols are toxic to the germinal cell layer of the seminiferous tubules when given to sham-irradiated mice.