Comparative mutagenesis by aminofluorene derivatives. A possible effect of DNA configuration.
The mutagenicity of N-acetoxy-N-2-acetylaminofluorene (N-acetoxy- 2AAF ) for Salmonella typhimuricum TA98 is greatly reduced when compared to that of N-hydroxy-2-aminofluorene. This decrease in mutagenic response is accompanied by the formation of a deoxyguanosine-2-acetylaminofluorene adduct. The deoxyguanosine-2-aminofluorene adduct, characteristic of cells exposed to N - hydroxy-2-aminofluorene, was not detected in N-acetoxy- 2AAF -treated cells. Enzymic deacetylation of N - acetoxy- 2AAF results in restoration of potent mutagenicity. N-Acetoxy-2-acetylamino-7- iodofluorene is also more mutagenic than N-acetoxy- 2AAF . Because the acetylated and unacetylated guanine adducts induce greatly different configurational changes, the results may be indicative that the introduction of the syn configuration and a possible shift to the Z-conformation at the mutational hot spot of Salmonella typhimurium TA98 [(dG-dC)8] results in reduced mutagenic potency.
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004269:DNA, Bacterial / Q000378:metabolism*; D005449:Fluorenes / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D009690:Nucleic Acid Conformation; D012486:Salmonella typhimurium / Q000187:drug effects; D013329:Structure-Activity Relationship
D004269:DNA, Bacterial; D005449:Fluorenes; D009153:Mutagens