Mutagenic activation of N-2-fluorenylacetamide and N-hydroxy-N-2-fluorenylacetamide in subcellular fractions from X/Gf mice.
The Salmonella mutagenesis test system was used to evaluate the in vitro mutagenic potency of N-2-fluorenylacetamide (2-FAA) and N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) mediated by liver and kidney subcellular fractions from X/Gf mice, a strain resistant to 2-FAA carcinogenesis. Pretreatment of the mice with the microsomal inducers 3-methylcholanthrene (MCA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased the number of revertants from both liver and kidney fractions. Mutagenicity of N-OH-2-FAA mediated by liver or kidney microsomes was partially inhibited at 0.001--0.1 microM Paraxon (diethyl-p-nitrophenyl phosphate), an inhibitor of deacetylase enzyme, and the inhibition was complete (98%) in microsomes from control mice (100 microM Paraoxon). Conversely, the liver and kidney microsomal fractions from MCA- and TCDD-treated X/Gf mice were less sensitive to Paraoxon. The inhibition of kidney or liver cytosol-mediated N-OH-2-FAA mutagenicity by Paraoxon was less than that observed with the microsomal fraction (50% inhibition at 1 x 10(-7) and 1 x 10(-5) M Paraoxon, respectively). The mutagenicity of 2-FAA and N-OH-2-FAA mediated by liver or kidney subcellular fractions from X/Gf mice and its response to inducers and inhibitors of mutagenic activation processes appear similar to those observed in species both resistant (cotton rat) and sensitive (Sprague-Dawley rat, NIH Swiss mice) to 2-FAA carcinogenesis.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D010261:Paraoxon / Q000494:pharmacology; D013347:Subcellular Fractions / Q000378:metabolism
D009153:Mutagens; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D010261:Paraoxon