DNA Cleavage Induced by Alkoxyl Radicals Generated in the Photolysis of N-Alkoxypyridinethiones

The photolysis of N-isopropoxypyridine-2-thione (1b) and of N-tert-butoxypyridine-2-thione (1c) generated alkoxyl radicals as confirmed by trapping experiments with DMPO and subsequent EPR spectroscopy. Upon UVA irradiation, the alkoxyl-radical sources induce strand breaks in supercoiled pBR 322 DNA, which was analyzed by gel electrophoresis. The participation of type I (electron transfer, H abstraction) or type II (1O2) photosensitization in the DNA cleavage by the oxyl-radical sources 1a–d or their photoproducts could be excluded. The present study establishes unequivocally that alkoxyl and benzoyloxyl, as well as hydroxyl radicals, cause strand breaks in DNA and, thus, may play a significant role in the DNA cleavage by peroxides.