Thymine Dimer Formation Mediated by the Photosensitizing Properties of Pharmaceutical Constituents

Thymine dimer formation is a major photochemical lesion of UV-irradiated DNA and has been implicated as a precursor in skin cancer. Certain pharmaceutical constituents, such as the sunscreen absorbers para-aminobenzoic acid, Uvinul DS49, Eusolex 232 and the tranquillizer chlorpromazine, have the potential to photosensitise thymine dimerisation in thymine-containing systems. The yields of thymine dimer, obtained from the UV-irradiation of thymine substrates in the presence of the photosensitisers, were determined by reverse phase HPLC. Computer simulations of the experimental results were used to establish the kinetics and mechanisms of photosensitised thymine dimerisation in the various systems investigated. Initial studies involved the photosensitisation of free thymine base in aqueous medium. In this system, sunscreen agents were found to be effective photosensitisers of thymine dimerisation. The PABA photosensitisation of thymine dimer formation in the more biologically relevant system, pUC19 plasmid DNA, was investigated. The kinetic mechanism for the photosensitised dimerisation of contiguous thymines in pUC19 plasmid DNA at pH 7 is reported.