1,4-Bis(2-[(2-hydroxyethyl)amino]ethylamino)-9,10-anthracenedione, an anthraquinone antitumour agent that does not cause lipid peroxidation in vivo; comparison with daunorubicin.

Daunorubicin administration to mice produces a marked stimulation of lipid peroxidation in both liver and heart 48 hours following administration. In direct contrast 1,4-Bis((2-[(2-hydroxyethyl)amino]ethylamino))-9,10-anthracenedione (HAQ) does not induce lipid peroxidation in the liver and actually inhibits this event in the heart. In addition, neither daunorubicin nor HAQ deplete reduced glutathione in liver or heart 48 hours after drug administration. Daunorubicin induced glutathione (GSH) depletion was observed 2.5 hours following administration. These results correlate with daunorubicin increased microsomal oxygen consumption whilst HAQ produced no measurable effect on the rate of microsomal oxygen utilisation. It would appear that redox cycling to produce free radical oxygen involved in lipid peroxidation and GSH depletion, an established action of daunorubicin, does not occur with HAQ. This apparent lack of HAQ reactivity may help explain the relatively low cardiotoxicity of this novel antitumour agent.