Formation of abasic sites in DNA by t-butyl peroxyl radicals: implication for potent genotoxicity of lipid peroxyl radicals.

We investigated abasic site formation in calf thymus DNA after exposure to a model compound of lipid-derived peroxyl radical that was generated by the reaction of tert-butyl hydroperoxide (t-BuOOH) with hemoglobin. Abasic site density in DNA was quantified by use of an enzyme-linked immunosorvent assay-like assay. In the presence of 10 mM t-BuOOH and 12.5 or 25 microM hemoglobin, 0.6-1.0 abasic sites/10(4) nucleotides were formed. However, abasic sites were not detected after replacing hemoglobin with nonheme iron, e.g. EDTA/Fe(2+), which initiates the production of alkyl and alkoxyl radicals. Therefore, the present results suggest that lipid peroxyl radicals may have a genotoxic potential through unique reactions, including depurination and depyrimidination, which lead to DNA strand breakage.