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.
Buc-Calderon
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P
Unité de Biochimie Toxicologique et Cancérologique, Ecole de Pharmacie, UCL 7369, Université Catholique de Louvain, Brussels, Belgium.
Defresne
M P
MP
Barvais
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C
Roberfroid
M
M
D000409:Alanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005609:Free Radicals; D006878:Hydroxides; D017665:Hydroxyl Radical; D008223:Lymphoma / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008815:Mice, Inbred Strains; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D009946:Organothiophosphorus Compounds / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D013481:Superoxides; D013997:Time Factors; D014965:X-Rays
D005609:Free Radicals; D006878:Hydroxides; D009946:Organothiophosphorus Compounds; D011837:Radiation-Protective Agents; D013481:Superoxides; C053274:AD 20; D017665:Hydroxyl Radical; D004999:Amifostine; D000409:Alanine