INACTIVATION AND MUTAGENESIS OF Herpes VIRUS BY PHOTODYNAMIC TREATMENT WITH THERAPEUTIC DYES

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Abstract
Dyes with photosensitize membranes may be clinically useful for photodynamic treatment (PDT) of Herpes simplex virus (SHV) infections. It is important to determine whether the enveloped HSV can be inactivated via membrane damage without affecting the genetic material. Selection of appropriate PDT conditions, including the choice of dye, could minimize viral mutagenesis. We determined the mutagenesis caused by PDT employing three membrane-photosensitizing dyes of potential use in cancer photochemotherapy (Photofrin II, polyhematoporphyrin esters, zinc phthalocyanine tetrasulfonates) and a DNA-photosensitizing dye (proflavine sulfate). The effects were compared to those caused by exposure of HSV to ultraviolet radiation (UV). the procedure consisted of incubating HSV with .mu.g/ml (.mu.M) concentrations of the dye, irradiating the samples with broad spectrum visible/near-UV radiation (Daylight fluorescent lamps) and assaying the survival of the treated HSV. Zinc phthalocyanine was the most potent dye per absorbed photon for inactivating HSV. In parallel with determination of survival, progeny of the surving virus were grown for determination of mutagenesis. The progeny virus was harvested and subsequently assayed in the presence and absence of 40 .mu.g/.mu.l iododeoxycytidine (ICrd) to determine the frequency of mutation to ICrd resistence. Mutation frequencies were determined for progeny from the 1-4% survival level. For PDT with each membrane-photosensitizing dye, only zinc phthalocyanine increased the mutation frequency over the untreated control. This increase was < 2-fold. Proflavine increased the mutation frequency 2-3 fold over the untreated control. Ultraviolet produced a 15-20 fold increase over the untreated control. Therefore, all four dyes were much less mutagenic than UV at the same toxicity level (P < 0.0001), and the membrane-photosensitizing dyes were less mutagenic than the DNA-photosensitizing proflavine at the same toxicity level (P < 0.0001).

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