MONOMERIC BASE DAMAGE PRODUCTS FROM ADENINE, GUANINE, AND THYMINE INDUCED BY EXPOSURE OF DNA TO ULTRAVIOLET-RADIATION

The formation of monomeric products in DNA upon exposure to UV radiati on was investigated, Three novel products were identified in DNA in aq ueous solution upon exposure to UV radiation at 254 nm in a dose range from 100 to 10 000 J/m(2), These were 4,6-diamino-5-formamidopyrimidi ne, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 5-hydroxy-5,6-dih ydrothymine. These three products are known to be substrates for base excision repair enzymes involved in the reversal of oxidative DNA dama ge. The dependence of the yields of formamidopyrimidines on UV radiati on dose was nonlinear, whereas the yield of 5-hydroxy-5,6-dihydrothymi ne was increased linearly in the entire dose range. Of these products, 4,6-diamino-5-formamidopyrimidine was the only compound produced in a ppreciable amounts at 310 nm. At the highest dose used, the formation of other pyrimidine- and purine-derived products was also observed, Th eir amounts, however, were increased above control levels up to 2-fold only. The hydroxyl radical scavenger dimethyl sulfoxide had no effect on product yields excluding the involvement of hydroxyl radical in pr oduct formation. 4,6-Diamino-5-formamidopyrimidine and 2,6-diamino-4-h ydroxy-5-formamidopyrimidine may be produced by hydration of adenine a nd guanine, respectively, across the N(7)-C(8) double bond by mechanis ms similar to those proposed previously for well-known formation of py rimidine hydrates with the hydroxyl group located at C(6). Formation o f 5-hydroxy-5,6-dihydrothymine indicates that hydration of thymine wit h the hydroxyl group located at C(5) of the pyrimidine ring also occur s, The results of these studies indicate that these monomeric base dam age products could be a biologically important component of the photop roducts that are responsible for the deleterious effects of UV radiati on.