Proflavin: an unusual mutagen.

In the Salmonella typhimurium mutagenicity assay, proflavin (PF), in the dark, was shown to possess some direct-acting frameshift mutagenic activity for strains TA1537 and TA98. In the presence of microsomal enzymes from mouse, hamster and rat livers, frameshift mutagenic activity for strain TA1538 and enhanced mutagenicity for strain TA1537 was observed. Exposure of bacteria to PF in the presence of visible light resulted in base substitution (strain TA1535) as well as frameshift (TA1537, TA1538, TA98) genetic activities. The findings are taken to indicate that PF possesses direct-acting frameshift activity (TA1537 and TA98) by virtue of its ability to intercalate between DNA base-pairs. The frameshift activity (TA1538, TA98 and enhanced TA1537) seen following metabolic or photo-activation may be due to the formation of chemical adducts between the cellular DNA and oxidation products of PF (a base-displacement effect). The light-induced base-substitution activity probably results from the generation of singlet oxygen which reacts with the guanine moiety of DNA. The mutagenic photoproduct of PF appears to be stable.