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.
Adam
W
W
Institute of Organic Chemistry, University of Würzburg, Germany. adam@chemie.uni-wuerzburg.de
Andler
S
S
Saha-Möller
C R
CR
D003497:Cyclic N-Oxides; D004249:DNA Damage; D004578:Electron Spin Resonance Spectroscopy; D008054:Lipid Peroxides / Q000737:chemistry* / Q000528:radiation effects; D009829:Oleic Acids / Q000737:chemistry* / Q000528:radiation effects; D010545:Peroxides / Q000737:chemistry* / Q000528:radiation effects; D010777:Photochemistry; D010957:Plasmids / Q000737:chemistry* / Q000528:radiation effects; D013113:Spin Labels; D014466:Ultraviolet Rays; D014970:Xanthines
D003497:Cyclic N-Oxides; D008054:Lipid Peroxides; D009829:Oleic Acids; D010545:Peroxides; D013113:Spin Labels; D014970:Xanthines; C103514:ethyl oleate hydroperoxide; C008464:methyl linoleate hydroperoxide; C017245:5,5-dimethyl-1-pyrroline-1-oxide