DNA Cleavage Induced by Oxyl Radicals Generated in the Photosensitized Decomposition of Fatty Ester Hydroperoxides Derived from Oleic and Linoleic Acid

The xanthone-sensitized photodecomposition of the fatty ester hydroperoxides 1 and 2 in the presence of pBR 322 DNA was investigated as a chemical model system to assess whether this process may cause DNA damage through oxyl radicals. Unequivocally, oxyl radicals are formed in the xanthone-sensitized photodecomposition of the hydroperoxides 1 and 2, as confirmed by EPR studies. Indeed, both hydroperoxides 1 and 2 induce DNA single-strand breaks upon uv-A irradiation in the presence of the exogenous sensitizer xanthone. Under similar reaction conditions, the corresponding alcohol 3 of the hydroperoxide 1 was ineffective. Mannitol as radical scavenger inhibited significantly the formation of DNA single-strand breaks in the xanthone-sensitized decomposition of the hydroperoxides 1 and 2. Irradiation of xanthone alone or the hydroperoxides 1 and 2 without sensitizer did not cause any detectable DNA single-strand breaks. These results confirm that photosensitization of the fatty ester hydroperoxides 1 and 2 induces DNA modifications by oxyl radicals. We suspect that the combination of endogenous photosensitizers, solar uv radiation, and lipid hydroperoxides may damage cellular DNA through oxyl radicals.