Anticlastogenic effect of S-2-(3-aminopropylamino) ethylphosphorothioic acid against X-rays in mice

The anticlastogenic effect of the aminothiol agent S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) against X-rays was assessed by in vivo mouse micronucleus assay. The frequency of micronuclei in the bone marrow of adult male Swiss mice treated with WR-2721, at a radioprotective dose of 200 mg/kg or 400 mg/kg body weight, 15 or 30 min before exposure to a sublethal dose of 6 Gy X-rays, was determined 24 h after X-irradiation. The protective effect of WR-2721 against X-ray-induced clastogenicity was shown in the erythropoietic system. WR-2721 administration prior to X-ray exposure was found to decrease the number of micronucleated polychromatic erythrocytes elevated by X-irradiation. The protection against the clastogenic activity of X-rays by WR-2721 was least evident when the thiol had been administered in the lower dose of 200 mg/kg body weight, 15 min before X-irradiation, and was most effective when giving WR-2721 in the higher dose, 400 mg/kg body weight, 30 min prior to exposure of mice to X-rays. Thus, the radioprotective effect of S-2-(3-aminopropylamino) ethylphosphorothioic acid against genotoxicity by X-rays appeared to depend on the dose given and the time intervals between WR-2721 administration and X-irradiation of mice. A novel clinical application of the drug could be in its use to protect against radiation-therapy-induced genotoxic damage to normal cells.