Evidence for the generation of free hydroxyl radicals from certain quinone antitumor antibiotics upon reductive activation in solution

Abstract

The nature of the reactive oxygen species generated from certain quinone antitumor antibiotics upon reductive activation in aqueous solution was investigated. A kinetic criterion was employed involving the relative rate of trapping of hydroxyl and formate radicals by the spin-trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) in conjunction with epr spectroscopy. By comparison with a system involving the photolysis of hydrogen peroxide as a standard free hydroxyl system it was concluded that at pH 7 and at 37 °C reductive activation of adriamycin, daunorubicin, mitomycin B, mitomycin C, and streptonigrin gives rise to free hydroxyl radicals in direct contrast with, for example, the photolysis of quinones in solution.