INDUCTION OF CROSS‐LINKS IN VIRAL DNA BY NATURALLY OCCURRING PHOTOSENSITIZERS

Abstract

Abstract— Six different photosensitizers were compared for their ability to form cross‐links in murine cellular DNA and murine cytomegalovirus DNA, in the presence of long wave UV radiation. The viral DNA was in the form of free DNA or intact virions. The compounds consisted of the linear furanocoumarins 8‐methoxypsoralen (8‐MOP) and isopimpinellin; the angular furanocoumarin, angelicin; the two furanochromones, visnagin and khellin; and the β‐carboline alkaloid, harmine. Cross‐linking was assessed by alkaline agarose gel electrophoresis and hydroxyapatite chromatography. 8‐MOP produced extensive cross‐linking (as expected), as did isopimpinellin. Visnagin produced less cross‐linking, such that not all DNA molecules were affected at the concentrations used. Khellin, angelicin and harmine produced no detectable cross‐linking. The same result was obtained for DNA which was treated in situ in the virion. To some degree there was a correlation between the amount of cross‐linking and the relative potency of anti‐MCMV infectivity. But other factors evidently contribute to the phototoxic effect of these compounds.