Effects of hydroxyl radical scavengers on relaxation of supercoiled DNA by aminomethyl-trimethyl-psoralen and monochromatic UVA photons

Abstract

The ability of scavengers of hydroxyl radical (OH radical) to modulate the photosensitized relaxation (induction of the first single-strand break) of supercoiled plasmid DNA with UVA photoactivated 4'-aminomethyl4,5',8-trimethylpsoralen was examined by comparing the dose reduction factor (DRF: the ratio of fluence required to induce the same degree of relaxation in the absence to the presence of OH radical scavengers). The addition of mannitol, azide, acetate, or formate at concentrations inversely proportional to the value of the rate constants for the scavenging of OH radicals partially attenuated the supercoiled DNA relaxation. The degrees of protection afforded by the four scavengers in the presence of AMT photoactivated by either 334 nm or 365 nm monochromatic photons were similar, giving an average DRF of about 0.25 in all cases. Given the diverse chemical nature of the scavengers and their wide range of concentrations utilized, these findings are evidence for the involvement of a Type I photosensitization in the induction of DNA single-strand breaks by photoactivated AMT.