Biological Evaluation of Radioprotective Drugs.
Annual rept. 1 Feb 86-31 Jan 87,
ANDERSON (M D) HOSPITAL AND TUMOR INST HOUSTON TX
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Our investigations of the mechanisms of radioprotection by aminothiols involve both in vitro and in vivo systems and utilize recent advances in the techniques of alkaline and neutral elution to measure the effect of aminothiols on the induction and rejoining of y-ray-induced DNA single-strand breaks SSBs and double-strain breaks DSBs, respectively. The resulting effects are correlated with the effects of the compound on cell survival. Both WR-1065 and WR-255591 protected against SSB and DSB induction in irradiated cultured cells, although to a lesser extent than the protection for cell survival. Both compounds also inhibited SSB but not DSB rejoining. In the mouse jejunum, WR-2721, WR-1065, and WR-3689 provided little protection against SSB induction at doses of drug that gave considerable protection in the jejunal microcolony assay each of the compounds retarded SSB rejoining. The cellular mechanisms resulting in radioprotection are apparently complex, and may involve qualitative as well as quantitative alterations in the DNA lesions induced by radiation several testable hypotheses are proposed in which the effects of the drug may be mediated via a direct interaction with DNA. Keywords radioprotective drugs, cultured, cells, mouse, jejunum, DNA, damage, repair, survival, drugs.