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MUTAGENICITY AND MUTATION SPECTRA OF 2-ACETYLAMINOFLUORENE AT FRAMESHIFT AND BASE-SUBSTITUTION ALLELES IN FOUR DNA REPAIR BACKGROUNDS OF SALMONELLA
Citation:
Shelton, M. AND D.M. DeMarini. MUTAGENICITY AND MUTATION SPECTRA OF 2-ACETYLAMINOFLUORENE AT FRAMESHIFT AND BASE-SUBSTITUTION ALLELES IN FOUR DNA REPAIR BACKGROUNDS OF SALMONELLA. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/305, 1995.
Description:
We used colony probe hybridization procedures-to determine the mutations in 600 revertants of the -1 frameshift allele hisD3052 and 200 revertants of the base substitution allele hisG46 of Salmonella typhimurium induced by 2-acetylaminofluorene (2-AAF) in the presence of S9. -AAF was primarily a frameshift mutagen, exhibiting 5 times more frameshift than base-substitution activity. he only frameshift mutation 2-AAF induced at the hisD3052 allele was a hotspot (-2) deletion within the sequence CGCGCGCG. he addition of the pKM101 plasmid had a small effect on the mutagenic potency of 2-AAF at this allele in a uvr background and no effect on the mutation spectra in either a uvr or uvr background. he small amount of base-substitution activity required the presence of both the pKM101 plasmid and the uvrb mutation. he base substitution were GC to TA transversions (86%) and GC to AT transitions (14%), and 85% of the substitutions were at the second position of the CCC target of the hisG46 allele; the remainder were at the first position. e propose that the hotspot frameshift may be initiated by N-acetyl-2-aminofluorene adducts located at the C(8) position of any of the guanines except the first one in the CGCGCGCG hotspot sequence. he mutation might then result from correct incorporation of cytosine opposite the adducted guanine, followed by a 2-base slippage according to our recently proposed model.