Alkaline labilization of DNA photosensitized by promazine derivatives

Superhelical pBR322 DNA has been photosensitized in the presence of various promazine derivatives. Agarose gel electrophoresis of the photosensitized DNA reveals that true single-strand breaks are induced during irradiation. Alkaline treatment of the photosensitized DNA with a subsequent alkaline agarose gel electrophoresis demonstrates that in addition to true single-strand breaks, these drugs can induce alkali-labile lesions. Although true single-strand breaks are induced randomly into a 5'-[32P]-end labeled pBR322 DNA fragments, the alkaline-labile alterations are located specifically at the level of guanine residues. A strong correlation seems to exist between the visualization of this labilization and the induction of a covalent photoadduct on guanine by the photosensitization mediated by PZ.