DNA oxidation induced by cyclooxygenase-2

The inducible form of cyclooxygenase, COX-2, has been shown to be overexpre ssed in various types of tumors, including colon and prostate cancer. Sever al studies indicate that COX-2 inhibition can be beneficial for the prevent ion of these types of cancer. Since COX-2 reactions involve production of r eactive oxygen radicals that can potentially damage biological macromolecul es, we explored the possibility that DNA and/or nucleosides can be oxidized during cyclooxygenase reactions. When DNA or nucleosides were incubated wi th COX-2 and arachidonic acid, a significant increase in the amount of 8-ox o-2 ' -deoxyguanosine was observed. This increase was enzyme-dependent and could be prevented by COX-2 inhibitors as well as by antioxidants. These da ta indicate that peroxyl radicals or other oxidized species formed during c onversion of arachidonic acid to prostaglandin Gz might be responsible for the observed oxidation. These results suggest also that overexpression of C OX-2 in inflammatory diseases places an additional burden on antioxidative defenses of the cell, which might contribute to DNA oxidation and the induc tion of mutations.