Role of the superoxide anion in the oxidative activation of the new antitumor drug BD40: a radiolysis study.

ABSTRACT

BD40, a new antitumor drug derived from 9-azaellipticine, is thought to have an oxygen-dependent metabolism in vivo. We have investigated the one-electron oxidation of this drug by gamma radiolysis using OH. free radicals as oxidants and the reaction of O2-. with the BD40 oxidized transient(s). The absorption spectrum of the one-electron oxidized free radical was determined by pulse radiolysis using OH. or N.3 as reactant. In the absence of O2 and O2-., the initial yield of disappearance of the drug is equal to 2.5 x 10(-7) mol J-1 independently of the initial concentration of the drug and of the dose rate. When BD40 is oxidized by OH. radicals in the presence of O2 and O2-., the yield is the same. This yield is halved if superoxide dismutase is present during irradiation. Superoxide anions do not react directly with the drug. Thus it is suggested that these radicals oxidize the BD40 free radical produced by oxidation with OH. Biological implications are discussed.