Oxidative DNA damage in the photolysis of N-hydroxy-2-pyridone, a specifichydroxyl-radical source

The photooxidative DNA damage by N-hydroxy-2-pyridone (1) is caused by hydr oxyl radicals, as confirmed by electron paramagnetic resonance studies with the spin trap 5,5-dimethylpyrroline N-oxide. Irradiation of the pyridone 1 at 300 nm induced strand breaks in supercoiled pBR322 DNA, while in calf-t hymus DNA and 2'-deoxyguanosine (dG), respectively, 8-oxoguanine and 8-oxo- 7,8-dihydro-2'-deoxyguanosine were formed. Time-dependent control experimen ts disclosed that photoproducts of pyridone 1, e.g. 2-pyridone (3), are not responsible for the modification of DNA, Also the photosensitization by th e pyridine-2-one chromophore was excluded, because N-methylpyridine-2-one ( 2), which cannot generate hydroxyl radicals, was ineffective in the photoox idation of DNA and dG, Thus, the photolysis of pyridone 1 serves as a speci fic source of hydroxyl radicals for DNA damage, both strand breaks and base modifications.