Photosensitized inactivation of infectious DNA by urocanic acid, indoleacrylic acid and rhodium complexes.

T Mohammad, I Tessman, H Morrison, M A Kennedy, S W Simmonds

Index: Photochem. Photobiol. 59(2) , 189-96, (1994)

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Abstract

Naked, infectious single-stranded (ss) and double-stranded (ds) DNA from phages S13 and G4 were irradiated with 308 nm UV radiation in the absence and presence of several photobiologically active compounds: E- and Z-urocanic acid (E- and Z-UA), their methyl esters (E- and Z-MU), E- and Z-indoleacrylic acid (E- and Z-IA), cis-dichloro-bis(1,10-phenanthroline)rhodium(III) chloride (cDCBPR) and tris(1,10-phenanthroline)rhodium (III) perchlorate (TPR). E-urocanic acid protects against cyclobutane pyrimidine dimer formation in ssDNA but concomitantly photosensitizes the formation of other lesions that inactivate ssDNA. Z-urocanic acid also protects ssDNA against such dimerization but without the associated sensitized damage. The methyl ester isomers behave similarly. There is no such differential activity observed for the IA isomers, both of which sensitize the inactivation of ssDNA. Photostationary state mixtures of both UA and IA efficiently sensitize the inactivation of dsDNA, and cDCBPR strongly protects ssDNA from UV damage, while TPR is a significant sensitizer. Both of these metal complexes sensitize the inactivation of dsDNA slightly. For all compounds, cyclobutane pyrimidine dimers were the predominant lethal lesions produced by sensitization of the dsDNA, but they were not the major lethal lesions created by sensitization of the ssDNA. In the case of dsDNA, both UA and IA created pyrimidine dimers with a high degree of potential for mutagenesis, as determined by an assay that monitors the frequency of mutations following the spontaneous deamination of cytosine in photodimers.