Analysis of fluoroquinolone-mediated photosensitization of 2 '-deoxyguanosine, calf thymus and cellular DNA: Determination of Type-I, Type-II and triplet-triplet energy transfer mechanism contribution

Fluoroquinolone (FQ) antibacterials are known to exhibit photosensitization properties leading to the formation of oxidative damage to DNA. In additio n, photoexcited lomefloxacin (Lome) was recently shown to induce the format ion of cyclobutane pyrimidine dimers via triplet-triplet energy transfer. T he present study is aimed at gaining further insights into the photosensiti zation mechanisms of several FQ including enoxacin (Enox), Lome, norfloxaci n (Norflo) and ofloxacin (Oflo), This was achieved by monitoring the format ion of DNA base degradation products upon UVA-mediated photosensitization o f 2 ' -deoxyguanosine, isolated and cellular DNA, Oflo and Norflo act mainl y via a Type-II mechanism whereas Lome and, to a lesser extent, Enox behave more like Type-I photosensitizers. However, the extent of oxidative damage was found to he relatively low. In contrast, it was found that cyclobutane thymine dimers represent the major class of damage induced by Enox, Lome a nd Norflo within isolated and cellular DNA upon UVA irradiation. This strik ing observation confirms that FQ are able to promote efficient triplet ener gy transfer to DNA, The levels of photosensitized formation of strand break s, alkali-labile sites and oxidative damage to cellular DNA, as measured by the comet assay, were confirmed to be rather low, Therefore, we propose th at the phototoxic effects of FQ are mostly accounted for energy transfer me chanism rather than by Type-I or -II photosensitization processes.