Induction of -2 frameshift mutations by 2-nitrofluorene, N-hydroxyacetylaminofluorene, and N-2-acetylaminofluorene in reversion assays in Escherichia coli strains differing in permeability and acetyltransferase activity.
The mutagenicity of 2-nitrofluorene (NF), N-hydroxyacetylaminofluorene (N-OH-AAF), and N-2-acetylaminofluorene (AAF) was measured in strains of Escherichia coli that contain a lacZ allele that reverts by -2 frameshift mutations from CG(5) to CG(4). Mutagenesis was compared in a strain having wild-type permeability and metabolism, a strain with increased permeability caused by a lipopolysaccharide-defective (LPS(d)) mutation, a strain with N- and O-acetyltransferase (NAT/OAT) activity conferred by the Salmonella nat gene on plasmid pYG219, and a strain carrying both an LPS(d) mutation and pYG219. The LPS(d) mutation facilitated the measurement of mutagenicity but was not absolutely required, in that lower levels of mutagenicity were detected in LPS(+) strains. The NAT/OAT activity conferred by pYG219 strongly potentiated the mutagenicity of NF and N-OH-AAF. Surprisingly, AAF was mutagenic in the NAT/OAT LPS(d) strain without an exogenous P450 metabolic activation system. Its activity may be ascribable to the detection of a directly mutagenic impurity by the highly sensitive strain or to a low level of metabolic activation by the bacteria under the assay conditions. The findings add to the evidence that the lacZ allele derived from E. coli strain CC109 is an effective indicator of -2 frameshift mutagenesis and that strains expressing high levels of NAT/OAT activity are highly sensitive in monitoring the mutagenicity of nitroarenes and aromatic amides.
Hoffmann
G R
GR
Cancérogenèse et Mutagenèse Moléculaire et Structurale, UPR 9003, Centre National de la Recherche Scientifique, 67400 Illkirch, France. ghoffmann@holycross.edu
Janel-Bintz
R
R
Fuchs
R P
RP
D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D000123:Acetyltransferases / Q000378:metabolism; D000483:Alleles; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics*; D005449:Fluorenes / Q000378:metabolism / Q000633:toxicity*; D016368:Frameshift Mutation; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D007763:Lac Operon; D010539:Permeability
D005449:Fluorenes; C019499:2-nitrofluorene; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D000123:Acetyltransferases