EPR Spin-trapping studies of the reaction of radicals derived from hydroperoxide tumour-promoters with nucleic acids and their components

Abstract

EPR spin trapping experiments using the spin trap Me₃CNO have been used to identify radicals formed on reaction of Bu^tO˙ and PhC(CH₃)₂O˙[generated from reaction of the tumour promoter compounds Bu^tO₂H and PhC(CH₃)₂O₂H with Ti^III] with a variety of pyrimidine and purine derivatives, as well as RNA and DNA. The observed radical adducts can be rationalized in terms of addition of the alkoxyl radical to the C₅–C₆ double bond of the pyrimidine base and ring positions on the purine derivatives, as well as hydrogen abstraction at the sugar moiety; the latter process is believed to be a minor pathway and may occur as a result of radical transfer from the base to sugar moieties. Comparison of the experimental data with that obtained previously with HO˙ shows that the Bu^tO˙ and PhC(CH₃)₂O˙ radicals exhibit different regioselectivities than the former species. Experiments carried out with DNA, RNA and polynucleosides provide direct evidence for alkoxyl radical attack on these macromolecules; such reactions may play a role in the tumour-promoting activity of these hydroperoxides.