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

Summary

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. The D₀ was increased from 1·1 ± 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 also increased the shoulder of the clonogenic-cell survival curve. Studies were done to measure the effects of these two different radioprotectors 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 following exposure. WR-2721 reduced the number of initial radiation-induced DNA single-strand breaks when given one-half hour before exposure; the time of maximum protection. In contrast, 16-16 dm PGE₂ given 1 hour before irradiation (the time required to afford maximum protection from radiation cytotoxicity) did not reduce the number of initial DNA breaks. Both agents impeded the rate of rejoining of DNA breaks with increasing time after irradiation. However, the relationship between these effects on the rate of strand rejoining and cell survival is unknown. These results suggest that either both agents are similarly distributed within the cells but the mechanisms of radioprotection are different, or the mechanisms by which these agents protect are similar, but the two agents affect different subcellular targets, the protection of which contributes to increased cell survival.