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 radiation was investigated, Three novel products were identified in DNA in aqueous 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-formamidopyrimidine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 5-hydroxy-5,6-dihydrothymine. These three products are known to be substrates for base excision repair enzymes involved in the reversal of oxidative DNA damage. The dependence of the yields of formamidopyrimidines on UV radiation dose was nonlinear, whereas the yield of 5-hydroxy-5,6-dihydrothymine was increased linearly in the entire dose range. Of these products, 4,6-diamino-5-formamidopyrimidine was the only compound produced in appreciable amounts at 310 nm. At the highest dose used, the formation of other pyrimidine- and purine-derived products was also observed, Their 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 product formation. 4,6-Diamino-5-formamidopyrimidine and 2,6-diamino-4-hydroxy-5-formamidopyrimidine may be produced by hydration of adenine and guanine, respectively, across the N(7)-C(8) double bond by mechanisms similar to those proposed previously for well-known formation of pyrimidine hydrates with the hydroxyl group located at C(6). Formation of 5-hydroxy-5,6-dihydrothymine indicates that hydration of thymine with the hydroxyl group located at C(5) of the pyrimidine ring also occurs, The results of these studies indicate that these monomeric base damage products could be a biologically important component of the photoproducts that are responsible for the deleterious effects of UV radiation.