Effect of aqueous free radicals and cis-dichlorodiammineplatinum(II) on radiation-induced base release from DNA.

The radiation-induced release of (Me-/sup 3/H)thymine residues from purified Escherichia coli DNA irradiated in aqueous solution has been characterized by gel filtration. This yield of thymine residues is reduced by the presence of t-butanol or cis-dichlorodiammineplatinum (II) (cis-DDP) when samples are equilibrated with air, N/sub 2/, or N/sub 2/O, with the one exception that the yield of thymine base is unaltered by the presence of cis-DDP in N/sub 2/O-gassed solution. The OH radical reaction with DNA is the major pathway leading to thymine residue release, and the Pt(III) intermediate reacts in an analogous fashion to liberate thymine base specifically. The Pt(I) intermediate, though at half the Pt(III) efficiency, also causes the specific release of thymine base. In aerated solutions, the degree of reduction in radiation-induced thymine residue release caused by cis-DDP is in excess of that expected due to the scavenging of OH radicals by this platinum complex. cis-DDP reduction of the thymine residue yields must involve a mechanism that operates in addition to the scavenging of the OH radical. The Pt(I) intermediate is assessed to be the most likely species involved in the radiation sensitization of hypoxic cells, and its effect on thymine residue release in these experiments ismore » evaluated.« less