DNA targeted UVA photosensitization: characterization of an extremely photopotent iodinated minor groove binding DNA ligand.

摘要: Abstract Previous studies have described UVA-induced DNA strand breakage at the binding sites of iodinated minor groove bisbenzimidazoles. The breakage, presumably mediated by carbon-centred ligand radical produced photodehalogenation, was also shown to be cytotoxic. earlier included a comparison three isomers, designated ortho -, meta - and para -iodoHoechst, efficiency photo-induction breaks in plasmid proved much higher for -isomer. We now extended isomers with respect photo-induced cytotoxicity K562 cells. Although relationship between extent nuclear uptake concentration medium similar assay situ dehalogenation drug-treated cells indicated that apparent cross-section -isomer greater than 5-fold -isomers. Also, analysis clonogenic survival data showed event associated -iodoHoechst more efficient mediator or -iodoHoechst. number events 50% cell-kill (1.23 ± 0.04 × 10 4 ) less (3.92 ± 0.29 × 10 (11.6 ± 0.90 × 10 isomers. Thus it is concluded photopotency which an important feature context its potential use clinical phototherapy, due not only UVA-mediated ligand, but cytotoxic potency per event.