In Vitro Studies on Longwave Ultraviolet Light-Dependent Reactions of the Skin Photosensitizer Chlorpromazine with Nucleic Acids, Purines and Pyrimidines

Inactivation of the Scrapie Agent by Ultraviolet Irradiation in the Presence of Chlorpromazine

“…irradiation (Speaker etal., 1980), did not inhibit scrapie infectivity. We can find no reports that TFP causes photosensitization in patients treated with this drug due to binding of TFP to nucleic acids, or any reports of studies that show nucleic acid binding in vitro as demonstrated for chlorpromazine (Kahn & Davis, 1970;Rosenthal etal., 1978).…”

“…radiation (Day & Diamattina, 1977;Fujita et al, 1981). Chlorpromazine reacts faster with single-stranded than with double-stranded nucleic acids (Kahn & Davis, 1970), and is able to alter the permeability of lipid bilayers by increased penetration through membrane lipids and proteins (Maoi et al, 1979;Ogido et al, 1981). Thus, chlorpromazine may penetrate cellular components more effectively than psoralens, inducing breaks in single-stranded nucleic acids.…”

Photochemical Inactivation of Deoxyribonucleic and Ribonucleic Acid Viruses by Chlorpromazine

“…WEE, HSV-1, and Pichinde viruses are inactivated totally (to levels undetectable by the assays described above) by exposure to the highintensity UV light for less than 1 to 2 min in the presence of 10 ,ug of chlorpromazine per ml, as shown in Fig. la.…”

“…The involvement of a photoreaction between chlorpromazine and nucleic acid in the above inactivations is supported by the known photoreactions between chlorpromazine and purified nucleic acids (2,10,11,16), by the properties of chlorpromazine as a photoactivated mutagen (12,14), by similarities with the psoralen system, and by the study of adenovirus inactivation by Day and Dimattina (3). In the latter work, chlorpromazine photoinactivation was both correlated with the production of DNA strand breaks and found susceptible to DNA repair (as inferred from a threefold more rapid inactivation when measured in repair-deficient host cells).…”

“…Many of the photosensitizing properties of chlorpromazine may in fact be explained by the finding that under long-wave UV irradiation it binds to ribonucleic acid, DNA, and purine and pyrimidine nucleic acid bases (2,10,11). Early work suggested the possibility that chlorpromazine intercalates into the DNA double helix (16), and more recently the interaction of the drug with nucleic acids was confirmed by studying the fluorescent spectral shifts resulting from long-wave UV irradiation of nucleic acids in its presence (10). Such biochemical reactions of chlorpromazine may involve the free radical which is produced by long-wave UV irradiation of the drug and which may remain stable for many months (4).…”