Cancer chemopreventive oltipraz generates superoxide anion radical

The cancer chemopreventive actions of oltipraz, a member of a class of 1,2-dithiolethiones, have been primarily associated with the induction of phase 2 enzymes mediated by a 41 bp enhancer element known as the anti-oxidant response element in the promoter regions of many phase 2 genes. It has been suggested that oxygen radical formation by oltipraz may be a critical mechanism by which it exerts chemoprevention. Therefore, in the present work, studies were performed to directly determine if oltipraz generates oxygen free radicals. Electron paramagnetic resonance (EPR) spin trapping demonstrated that oltipraz slowly reacts in the presence of oxygen to generate the superoxide anion radical. This formation of superoxide by oltipraz was concentration- and time-dependent. EPR oximetry studies showed that oxygen was also slowly consumed paralleling the process of superoxide formation. Thus, oltipraz induced superoxide formation occurs and could be involved in the mechanism by which it exerts chemoprotection.