The effects of metabolic activation on the mutagenicity of aminoacridines.

Abstract

The mutagenic activity of a series of aminoacridines was examined by the preincubation method with and without mammalian metabolizing enzymes in Salmonella tester strains. Without metabolizing enzymes, three acridines having an amino substituent at position 9 showed high activity in Salmonella typhimurium TA1537 and TA1977, and other acridines with amino substituents at position 2 or 3 were mutagenic but were less effective than the 9-aminoanalogs. The liver microsomal enzymes generally deactivated acridine mutagenicity in TA1537, but created a broad spectrum of mutagenicity if tested by the reversion of TA1535, the strain detecting base-pair substitution mutagens, and TA 1538, the strain detecting covalently bound frameshift mutagens.