Induction of-2 frameshift mutations by 2-nitrofluorene, N-hydroxyacetylamino-fluorene, and N-2-acetylaminofluorene in reversion assays in Escherichiacoli strains differing in permeability and acetyltransferase activity

The mutagenicity of 2-nitrofluorene (NF), N-hydroxyacetylaminofluorene (N-O H-AAF), and N-2-acetylaminofluorene (AAF) was measured in strains of Escher ichia coli that contain a lacZ allele that reverts by -2 frameshift mutatio ns from CG(5) to CG(4). Mutagenesis was compared in a strain having wild-ty pe permeability and metabolism, a strain with increased permeability caused by a lipopolysaccharide-defective (LPSd) mutation, a strain with N- and O- acetyltransferase (NAT/OAT) activity conferred by the Salmonella naf gene o n plasmid pYG219, and a strain carrying both an LPSd mutation and pYG219. T he LPSd mutation facilitated the measurement of mutagenicity but was not ab solutely required, in that lower levels of mutagenicity were detected in LP S+ strains. The NAT/OAT activity conferred by pYG219 strongly potentiated t he mutagenicity of NF and N-OH-AAF Surprisingly, AAF was mutagenic in the N AT/OAT LPSd strain without an exogenous P450 metabolic activation system. I ts activity may be ascribable to the detection of a directly mutagenic impu rity by the highly sensitive strain or to a low level of metabolic activati on by the bacteria under the assay conditions. The findings add to the evid ence that the lacZ allele derived from E. coli strain CC109 is an effective indicator of -2 frameshift mutagenesis and that strains expressing high le vels of NAT/OAT activity are highly sensitive in monitoring the mutagenicit y of nitroarenes and aromatic amides. (C) 2001 Elsevier Science B.V. All ri ghts reserved.