REDUCTION OF ANTITUMOR MITOSENES IN NONAQUEOUS AND AQUEOUS ENVIRONMENT - AN ELECTRON-SPIN-RESONANCE AND CYCLIC VOLTAMMETRY STUDY

Chemical reduction of mitosenes under aerobic conditions in DMSO showe d characteristic ESR signals of the mitosene derived semiquinone free radicals. However, these signals diminished strongly upon addition of water to the reaction mixture, indicating a short lifetime of the mito sene semiquinone free radicals under aqueous conditions. In addition, enzymatic one-electron reduction of these mitosenes with either xanthi ne oxidase or purified NADPH cytochrome P450 reductase under anaerobic conditions showed no signals of the mitosene semiquinone free radical s. Subsequent cyclic voltammetry measurements demonstrated facilitatio n of the further one-electron reduction of the mitosene semiquinone fr ee radicals in the presence of water in comparison with non-aqueous co nditions. The present results strongly suggest that in the presence of water relatively stable hydroquinones are formed upon reduction of mi tosenes. Consequently, the steady state concentrations of mitosene sem iquinone free radicals will be lowered substantially in aqueous enviro nment. Thus under physiological conditions, two-electron reduction and formation of the mitosene hydroquinone might be important in processe s leading to DNA alkylation by these mitosenes.