MUTAGENICITY OF ACRIDINES IN A REVERSION ASSAY BASED ON TETRACYCLINE RESISTANCE IN PLASMID PBR322 IN ESCHERICHIA-COLI

The mutagenicity of a series of acridine compounds was studied in an a ssay based on the reversion of mutations in the tetracycline-resistanc e gene (tet) of plasmid pBR322 in Escherichia coli. Mutations that res tore the tetracycline-resistant phenotype were detected in tetracyclin e-sensitive strains carrying mutant plasmids. Mutations that revert by +2, +1, -1, and -2 frameshift mutations and by base-pair substitution s were used to analyze the mutagenicity of two simple acridines, two a cridine mustards, and a nitroacridine. The simple acridines (9-aminoac ridine and quinacrine) effectively induced -1 frameshifts and weakly i nduced +1 frameshifts. The acridine mustards (quinacrine mustard and I CR-191) were more potent inducers of -1 and +1 frameshifts than the si mple acridines. Reactive acridines, including both the mustards and th e nitroacridine Entozon, were effective inducers of -2 frameshifts but the simple acridines were not The two classes of reactive acridines d iffered from one another, in that the mustards were better inducers of +1 frameshifts than Entozon, whereas Entozon was a particularly poten t inducer of -2 frameshifts. None of the compounds induced +2 frameshi fts, and the induction of base-pair substitutions was negligible. Thes e results confirm and extend studies showing that adduct-forming acrid ines are stronger frameshift mutagens than simple intercalating acridi nes and that the acridines differ from one another not only in overall mutagenic potency but also in the prevalence of different classes of frameshift mutations.