PULSE-RADIOLYSIS STUDIES ON THE OXIDATION OF OH(CENTER-DOT)RADICAL-DAMAGED DNA BY NITROQUINOLINES IN AQUEOUS-SOLUTION

The reactions of nitroquinolines with radical sites on DNA, formed by OH. radical attack in aqueous solution, have been studied. It is found that the small concentrations of compound, unbound to DNA, oxidise the essentially immobile DNA radicals with diffusion-controlled rate constants of ca. 5 x 10(9) dm(3) mol(-1) s(-1) to form absorbing radical anions. Oxidation of the radical sites by the proportion of the compounds bound to DNA does not occur, except to a small extent in the case of the 6-nitro regioisomer. Calculations based on the measured intrinsic association constant and migration rate along DNA of the 6-nitro regioisomer yield a jump time between neighbouring sites on the DNA of 2.76 ns. Competition studies between such compounds which bind to DNA and xenobiotica for OH. radical-damaged sites on DNA is illustrated by studies with three thiol compounds which yield second-order rate constants for repair of the DNA radicals, through H-atom donation; glutathione, 1.2 x 10(6) dm(3) mol(-1) s(-1), cysteine, 6 x 10(6) dm(3) mol(-1) s(-1) and cysteamine, 1.6 x 10(8) dm(3) mol(-1) s(-1).