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 hydroper oxides 1 and 2 in the presence of PER 322 DNA was investigated as a ch emical model system to assess whether this process may cause DNA damag e through oxyl radicals. Unequivocally, oxyl radicals are formed in th e xanthone-sensitized photodecomposition of the hydroperoxides 1 and 2 , as confirmed by EPR studies. Indeed, both hydroperoxides 1 and 2 ind uce 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. Ma nnitol as radical scavenger inhibited significantly the formation of D NA single-strand breaks in the xanthone-sensitized decomposition of th e hydroperoxides 1 and 2. Irradiation of xanthone alone or the hydrope roxides 1 and 2 without sensitizer did not cause any detectable DNA si ngle-strand breaks. These results confirm that photosensitization of t he fatty ester hydroperoxides 1 and 2 induces DNA modifications by oxy l radicals. We suspect that the combination of endogenous photosensiti zers, solar uv radiation, and lipid hydroperoxides may damage cellular DNA through oxyl radicals. (C) 1998 Academic Press.