Oxidized apurinic/apyrimidinic sites formed in DNa by oxidative mutagens

Abstract

Treatmetn of DNa with any of several agents, including ionizing radiation, hydrogen peroxide, bleomycin, neocarzinostatin and the copper (I) chelate complex of 1,10-phenantroline, produces apurinic/apyrimidinic (AP) sites containing oxidized deoxyribose moieties. These AP sites, which are formed by specific or nonspecific free-radical attack on deoxyribose, have been shown to involve oxidation of deoxyribose at the C-1′, C-2′ or C-4′ position. Oxidized AP sites are generally more susceptible to chemical cleavage than normal AP sites, but are in some cases resistant to cleavage by repair AP endonucleases. Nearly all of the AP sites produced by neocarzinostatin, and a fraction of those produced by bleomycin, are accompanied by closely opposed breaks in the complementary strand. Sequence specificity data strongly implicate oxidized AP sites in neocarzinostatin-induced mutagenesis. The role of AP sites in mutagenesis by the other oxidative mutagens is less clear, although there is in some cases suggestive evidence for such a role.