Identification of new scavengers for hydroxyl radicals and superoxide dismutase by utilising ultraviolet A photoreaction of 8-methoxypsoralen and a variety of mutants of Escherichia coli: Implications on certain diseases of DNA repair deficiency

摘要

8-Methoxypsoralen + UVA (ultraviolet light of 320-400 nm) known as PUVA has been in use for a number of years for the treatment of psoriasis and vitiligo. The treatment possibly works on the basis of UVA photoactivated 8-methoxypsoralen binding to DNA forming both single strand and double strand type damage. We have used Escherichia coli as model system in studying PUVA induced DNA damage and repair. It has been known for some time that the photoactivated 8-methoxypsoralen, besides intercalating with DNA, generates at least two reactive oxygen species (ROS): hydroxyl radicals and superoxide anions, and also singlet oxygen. In this study it has been found that, in E. coli, malate dehydrogenase, succinate dehydrogenase and NADH:ubiquinone oxidoreductase can protect cells from PUVA killing presumably by scavenging these ROS. Possible mechanisms have been proposed for these enzymes as cell protectors. Studies also suggest the potential for the use of PUVA in the treatment of a large number of human diseases. This study also finds that, unlike 8-methoxypsoralen, trioxsalen (4,5',8-trimethylpsoralen, another derivative of psoralens) does not generate ROS by UVA photoactivation; and hence the mode of action of trioxsalen and PUVA overlaps only in the binding of these molecules to DNA in the presence of UVA.