RADIATION ACTIVATION OF CARCINOGENS AND THE ROLE OF OH AND O2-

Abstract— Radiation-induced covalent binding of labelled carcinogens to DNA has been investigated under a variety of conditions using ultrafiltration or millipore filtration of TCA precipitable complexes. High yields of carcinogen binding at high DNA concentrations are also observed for a variety of small molecules and are not carcinogen-specific. At high carcinogen concentrations, radiation-induced unstable electrophilic carcinogenic species are produced, and undergo free-radical reactions which simulate cellular redox reactions involved in metabolic carcinogen activation, leading to the formation of covalently bound carcinogen adducts to DNA as a potential target macromolecule. The yields of carcinogen-DNA adducts increase linearly with dose and depend upon carcinogen concentration. The results of scavenger studies indicate that the oxidising species O₂^- and OH are the principal activating species. Rate constants for the selective radiation-induced oxidation reactions of various chemical carcinogens with superoxide have been measured by a competition kinetic method using pulse radiolysis. The relatively long-lived superoxide radical reacts with carcinogens at a rate which is two orders of magnitude slower than the diffusion-controlled rate for the hydroxyl radical, thus allowing a measure of O₂^- specificity in the presence of competing reactants within the cell.