N-acyl dehydroalanines protect from radiation toxicity and inhibit radiation carcinogenesis in mice.

N-Acyl dehydroalanines have shown free radical scavenging activity. They react with and scavenge mainly oxygen-derived free radicals such as the superoxide anion (O2-.) and the hydroxyl radical (HO.). Ortho-methoxyphenylacetyl dehydroalanine (AD-20) protects total-body irradiated mice against the toxicity induced by X-rays when delivered as a single dose of 700 rads in a short period of time. This degree of protection was of the same order of magnitude as that obtained with the aminothiol S-2-(3-aminopropylamino)-ethylphosphorothioic acid (WR-2721). The radioprotection of AD-20 is extended to all other doses of X-rays tested (from 600 to 800 rads). Furthermore, AD-20 inhibits the development of thymic lymphomas in C57Bl/Ka mice undergoing a leukaemogenic course of irradiation (4 x 175 rads applied at weekly intervals). We postulate that AD-20 may act as a radioprotector and anticarcinogenic agent, most probably by inactivating the oxygen-derived free radicals formed during water radiolysis.