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

Abstract
N-Acyl dehydroalanines have shown free radical scavenging activity. They react with and scavenge mainly oxygen-derived free radicals such as the superoxide ank>n (O-) 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 add (WR-2721). The radioprotectkm 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 C57B1/Ka mice undergoing a leukaemogenic course of irradiation (4 × 175 rads applied at weekly intervals). We postulate that AD-20 may act as a radioprotector and anticarcinogenk agent, most probably by inactivating the oxygen-derived free radicals formed during water radiolysis.