title: Frameshift mutations induced by three classes of acridines in the lacZ reversion assay in Escherichia coli: potency of responses and relationship to slipped mispairing models.
abstract: The frameshift mutagenicity of 9-aminoacridine (9AA) was compared with that of quinacrine, the acridine mustards ICR-191 and quinacrine mustard (QM), and the nitroacridine Entozon in the lacZ reversion assay in Escherichia coli. As intercalating agents, 9AA and quinacrine cause mutations through noncovalent associations with DNA. Mustards and nitroacridines form covalent adducts in DNA and give rise to different spectra of mutations. Quinacrine and 9AA most effectively induced -1 frameshifts in a run of guanine residues, with 9AA being the more potent mutagen. They also induced +G frameshifts. The acridine mustard ICR-191 was a stronger mutagen than 9AA, owing largely to its potent induction of +G frameshifts. QM induced +G frameshifts more strongly than did its nonreactive counterpart quinacrine. The nitroacridine Entozon differed from the other acridines in being a potent inducer of -2 frameshifts, but it was less effective in inducing +/-1 frameshifts. Quinacrine, although a simple intercalator, induced all five kinds of frameshift mutations detected in the assay, as did the acridine mustards. Although +A and -A frameshifts were induced, adenine runs were less susceptible to acridine mutagenesis than guanine runs. The patterns of frameshift mutagenicity in the lacZ assay are similar to those in an assay based on the reversion of mutations in the tetracycline-resistance gene of the plasmid pBR322. The similarity suggests that the responses reflect the inherent bacterial mutagenicity of the compounds in the local sequence context and are not highly dependent on the broader sequence context. The results are interpreted with respect to slipped mispairing models of frameshift mutagenesis.
authors.affiliation: Department of Biology, College of the Holy Cross, Worcester, Massachusetts 01610, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Hoffmann
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Calciano
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Lawless
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mahoney
mesh_terms: D000166:Acridines / Q000633:toxicity*; D000585:Aminacrine / Q000633:toxicity; D000609:Aminoacridines / Q000633:toxicity; D004926:Escherichia coli / Q000235:genetics; D016368:Frameshift Mutation; D007364:Intercalating Agents / Q000633:toxicity; D007763:Lac Operon; D008957:Models, Genetic; D009152:Mutagenicity Tests; D009588:Nitrogen Mustard Compounds / Q000633:toxicity; D011796:Quinacrine / Q000633:toxicity
chemical_list: D000166:Acridines; D000609:Aminoacridines; C477695:Entozon; D007364:Intercalating Agents; D009588:Nitrogen Mustard Compounds; C091910:acridine mustard; D000585:Aminacrine; D011796:Quinacrine