Radiation-induced DNA single-strand breaks in the intestinal mucosal cells of mice treated with the radioprotectors WR-2721 or 16-16 dimethyl prostaglandin E2

Both S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR-2721) and 16-16 dimethyl prostaglandin E2 (dm PGE2) protected the intestinal clonogenic cells to some degree from the effects of 137Cs γ-irradiation. Dsub(o) was increased from 1.1 to + -0.12 Gy in controls to 1.55 + = 0.48 Gy in 16-16 dm PGE2 treated and 2.12 + -0.20 Gy in WR-2721 treated mice. Both agents increased the shoulder of the clonogenic-cell survival curve. The effects of these different radioprotectors were measured on radiation-induction of DNA single-strand breaks in cells comprising the murine intestinal mucosa. The number of DNA single-strand breaks increased with increasing doses of γ-rays in animals killed immediately after exposure. WR-2721 reduced the number of initial radiation-induced DNA single-strand breaks when given one-half hour before exposure, (maximum protection). In contrast, 16-16 dm PGE2 given 1 hour before irradiation (time of maximum protection from radiation cytotoxicity) did not reduce the number of initial DNA breaks. Both impeded the rate of rejoining of DNA breaks with increasing time after irradiation. The relationship between these effects on the rate of strand rejoining and cell survival is unknown. (author)