Xanthone-sensitized photo-oxidation of guanine in calf thymus DNA and in the nucleoside 2'-deoxyguanosine has been investigated in the presence of various additives, with major emphasis on hydroperoxides. The formation of the guanine oxidation products 7,8-dihydro-8-oxoguanine (8-oxoGua), which is a marker for oxidative DNA damage, and 2,2-diamino-4-[(2-deoxy-beta-D-erythro-pentofuranosyl)amino]-5(2H)-oxazo lone (oxazolone) was monitored quantitatively by high performance liquid chromatography electrochemical or fluorescence analysis. Irradiation (350 nm) of calf thymus DNA in the presence of xanthone as sensitizer afforded 8-oxoGua in 1.4% yield. The ethyl oleate hydroperoxide 1a and its alcohol 1b inhibit the formation of 8-oxoGua very efficiently (up to 85%). Even the structurally simple t-butyl hydroperoxide and the physiologically relevant hydrogen peroxide exhibit strong inhibition of photosensitized oxidation of guanine in DNA and in the nucleoside, while t-butanol and the allylic alcohols 3b and 4 do not. Hydroperoxides in general quench type I-sensitized (benzophenone, xanthone) photo-oxidation of guanine, but not that of rose bengal, a predominant type II sensitizer. The inhibiting effect is explained by H abstraction of the electronically excited carbonyl chromophore from the additive. The biological relevance of these findings should be seen in the potential protecting role of lipid hydroperoxides and their corresponding alcohols against oxidative stress.