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Savoye, C ; Swenberg, C ; Hugot, S ; Sy, D ; Sabattier, R ; Charlier, M ; Spotheim-Maurizot, M

Thiol WR-1065 and disulphide WR-33278, two metabolites of the drug ethyol (WR-2721), protect DNA against fast neutron-induced strand breakage

International Journal of Radiation Biology 71 (2) 193-202

par Administrateur - publié le , mis à jour le

Abstract :

The main metabolites of the cytoprotective drug Ethyol (Amifostine, WR-2721) are the thiol WR-1065 and the disulphide WR-33278 (formed by the oxidation of WR-1065). Both metabolites are well-known protectors against DNA damage induced by gamma-rays. Using supercoiled plasmid DNA and restriction fragments we show that they protect efficiently also in the case of fast neutrons. In anoxic conditions WR-1065 (Z = +2) protects by scavenging of OH. and by ’chemical repair’ (by H donation from its SH function). WR-33278 (Z = +4) protects by scavenging of OH. and, in the case of the supercoiled plasmid DNA, by reducing the accessibility of radiolytic attack sites via the induction of packaging of DNA in liquid-crystalline condensates (observed by circular dichroism).