GENETIC TOXICITY OF 2-ACETYLAMINOFLUORENE, 2-AMINOFLUORENE AND SOME OF THEIR METABOLITES AND MODEL METABOLITES

2-Acetylaminofluorene and 2-aminofluorene are among the most intensively studied of all chemical mutagens and carcinogens. Fundamental research findings concerning the metabolism of 2-acetylaminofluorene to electrophilic derivatives, the interaction of these derivatives with DNA, and the carcinogenic and mutagenic responses that are associated with the resulting DNA damage have formed the foundation upon which much of genetic toxicity testing is based. The parent compounds and their proximate and ultimate mutagenic and carcinogenic derivatives have been evaluated in a variety of prokaryotic and eukaryotic assays for mutagenesis and DNA damage. The reactive derivatives are active in virtually all systems, while 2-acetylaminofluorene and 2-aminofluorene are active in most systems that provide adequate metabolic activation. Knowledge of the structures of the DNA adducts formed by 2-acetylaminofluorene and 2-aminofluorene, the effects of the adducts on DNA conformation and synthesis, adduct distribution in tissues, cells and DNA, and adduct repair have been used to develop hypotheses to understand the genotoxic and carcinogenic effects of these compounds. Molecular analysis of mutations produced in cell-free, bacterial, in vitro mammalian, and intact animal systems have recently been used to extend these hypotheses.