Singlet oxygen induces oxidation of cellular DNA

The aim of the present work was to evaluate the potential for O-1(2) to ind uce oxidation of cellular DNA. For this purpose cells were incubated in the presence of a water-soluble endoperoxide whose thermal decomposition leads to the formation of singlet oxygen. Thereafter, DNA was extracted and the level of several modified DNA bases was determined by HPLC analysis coupled to a tandem mass spectrometric detection. A significant increase in the le vel of 8-oxo-7,8-dihydro-2'-deoxyguanosine was observed upon incubation of the cells with the chemical generator of O-1(2), whereas the level of the o ther DNA bases measured remained unchanged. To demonstrate that singlet oxy gen is directly involved in the formation of 8-oxo-7,8-dihydro-2'-deoxyguan osine, the corresponding O-18-labeled endoperoxide was used. Incubation of the cells with such a generator of O-18-labeled singlet oxygen results in t he formation of O-18-labeled 8-oxo-7,8-dihydro-2'-deoxyguanosine in the nuc lear DNA. This result clearly demonstrates that singlet oxygen, when releas ed within cells, is able to directly oxidize cellular DNA.