Extracellular metabolites of 2-aminofluorene in cultures of rapid and slow acetylator rabbit hepatocytes as a model for urinary and biliary metabolism.

  title={Extracellular metabolites of 2-aminofluorene in cultures of rapid and slow acetylator rabbit hepatocytes as a model for urinary and biliary metabolism.},
  author={Charlene A. Mcqueen and M J Miller and B M Way and G. M. Williams},
  journal={Chemico-biological interactions},
  volume={66 1-2},
2 Citations
MEIC—A new international multicenter project to evaluate the relevance to human toxicity of in vitro cytotoxicity tests
A new international project to evaluate the relevance for human systemic and local toxicity of in vitro tests of general toxicity of chemicals has been organized by the Scandinavian Society of Cell


Species differences in the metabolism of 2-acetylaminofluorene by hepatocytes in primary monolayer culture.
The balance between activation and detoxification reactions of AAF in hepatocytes may be expressed as the ratio between covalently bound metabolites and the sum of C-hydroxylated and stable water-soluble metabolites, which correlated better with the species susceptibility to liver cancer than covalent binding as such.
Determination of host genetic susceptibility to genotoxic chemicals in hepatocyte cultures.
The identification of phenotype-dependent differences in the amount of DNA damage in rabbit hepatocytes offers evidence for genetic susceptibility to genotoxic chemicals and indicates that a similar susceptibility would be displayed by humans who express the same polymorphism in NAT activity.
Formation, metabolic activation by N, O-acyltransfer, and hydrolysis of N-acyl-N-arylamine derivatives.
The extreme genetic differences in the levels of the enzymes involved in the metabolism of N-acyl derivatives of arylamines in man and experimental animals offers an experimental approach that may aid in elucidating the mechanisms by which these compounds induce cancer.
Metabolism and binding of benzo(a)pyrene and 2-acetylaminofluorene by short-term organ cultures of human and rat bladder.
Both human and rat bladder epithelium can metabolize known potent carcinogens and, in the case of BP, can effect covalent binding between the products of metabolism and the urothelial cell DNA, demonstrating that carcinogenesis in the urinary bladder could thus be initiated by carcinogens produced or excreted in the urine without the necessity for their prior metabolism elsewhere in the body.
Multiple N-acetyltransferases and drug metabolism. Tissue distribution, characterization and significance of mammalian N-acetyltransferase.
Studies in vitro and in vivo with both ;rapid' and ;slow' acetylator rabbits revealed that, for certain substrates, extrahepatic N-acetyltransferase contributes significantly to the total acetylating capacity of the individual.
Mutagenic activation of N-hydroxy-2-acetylaminofluorene in the Salmonella test system: the role of deacetylation by liver and kidney fractions from mouse and rat.
The data indicate that deacetylation is the most important step in the mutagenic activation of N-hydroxy-2-acetylaminofluorene by mouse and rat liver and kidney fractions and that the arylnitrenium ion is the electrophilic species interacting with the bacterial DNA, resulting in the frameshift mutation.
N-hydroxy-2-acetylaminofluorene sulfotransferase: its probable role in carcinogenesis and in protein-(methion-S-yl) binding in rat liver.
The results strongly suggest that AAF-N-sulfate is at least one of the ultimate reactive and carcinogenic metabolites of AAF and N-hydroxy-AAF in rat liver.
The oxidation of 2-aminofluorene by prostaglandin endoperoxide synthetase. Comparison with other peroxidases.
Results suggest that 2-AF is oxidized to an electrophilic intermediate(s) by prostaglandin endoperoxide synthetase, which either binds covalently to tissue macromolecules or is further rapidly oxidizing to 2-nitrofluorene and azofluorene.
Metabolism and DNA adduct formation of 2-acetylaminofluorene by bladder explants from human, dog, monkey, hamster and rat.
It is concluded that bladder explants of the human, dog, monkey, hamster and rat metabolize AAF mainly to ring-hydroxylated products, but also form small amounts of the proximate carcinogenic metabolite N-hydroxy-AAF.