Radiation-induced peroxidation of DNA and effects of redox-active agents

With nucleic acids present as solutes in the irradiated solutions the chemical evidence, reviewed briefly below, is that the observed peroxidation is associated with hydroxyhydroperoxides formed on the pyrimidine components of polynucleotides. Such peroxidation of DNA has long interested radiobiologists in view of its possible relevance to the well-known oxygen effect in radiation biology, viz., the marked sensitizing effects of oxygen on radiation damage to living cells. In this connection questions arise concerning the post-irradiation fate of the hydroxyhydroperoxides produced in situ on the genetic material. If this were to involve some metal-ion catalyzed decomposition (e.g., by transition metal cations) there is the possibility that this could lead to further radical-initiated DNA lesions. With this possibility in mind we considerd it of interest, in the first instance, to investigate the effects of some transition metal ions on the stability of hydroxyhydroperoxides produced on irradiation of various pyrimidine compounds and polynucleotides, and some of our results are presented in the second part of this paper. Finally, we present some preliminary results on the effect of bleomycin, a redox-active anticancer drug, on DNA hydroxyhydroperoxide. 16 refs., 2 figs