Activation of N-acetoxy- and N-hydroxy-2-acetylaminofluorene to mutagenic and cytotoxic metabolites by V79 Chinese hamster cells.
N-Acetoxy-2-acetylaminofluorene (AAAF) and N-hydroxy-2-acetylaminofluorene (OH-AAF) are mutagenic to V79 cells, causing the induction of 6-thioguanine-resistant clones, and are cytotoxic. The presence of the deacetylase inhibitor, paraoxon, drastically reduces both the mutagenic and cytotoxic effects. This strongly suggests that deacetylated metabolites are the major active species. Furthermore, when Salmonella typhimurium TA98 is used as target organism, addition of homogenate of V79 cells strongly potentiates the mutagenicity of OH-AAF. To our knowledge, this is the first report demonstrating a significant biological effect due to the metabolism of a mutagen by V79 cells.
D015073:2-Acetylaminofluorene / Q000031:analogs & derivatives*; D000099:Acetoxyacetylaminofluorene / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D010261:Paraoxon / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects
D009153:Mutagens; D006881:Hydroxyacetylaminofluorene; D000099:Acetoxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D010261:Paraoxon