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Sex differences in the biotransformation of 2-acetylaminofluorene in cultured rat hepatocytes

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Sex-related differences in susceptability to 2-acetylaminofluorene (2-AAF) hepatocarcinogenicity and in vivo biotransformation of 2-AAF have been observed. In order to determine the contribution of hepatocytes to these differences, 2-AAF biotransformation was investigated in monolayer cultures of hepatocytes freshly isolated from male and female F-344 rats.

In cultured hepatocytes from both sexes, ring and N-hydroxylated, deacetylated and conjugated metabolites were formed. The half-life of 2-AAF was similar at concentrations of 5×10−6 and 10−5 M; however, at 10−4 M a slower rate was observed in cultures from males. Although the total formation of aqueous metabolites was similar, the ratio of sulfate to glucuronide conjugates of 2-AAF formed by hepatocytes from male and female rats differed. Sulfate conjugates predominated in hepatocytes from male rats, whereas in females, glucuronides predominated. The demonstration of sex-dependent variations in the rate of metabolism at a high concentration of 2-AAF and in conjugation provides evidence that in vivo differences are a function, at least in part, of the biotransformation characteristics of hepatocytes.

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Abbreviations

2-AAF:

2-acetylaminofluorene

2AF:

2-aminofluorene

WME:

Williams Medium E.

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Authors and Affiliations

  1. American Health Foundation, Valhalla, New York

    Charlene A. McQueen, Mary Jo Miller & Gary M. Williams

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  1. Charlene A. McQueen
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  2. Mary Jo Miller
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McQueen, C.A., Miller, M.J. & Williams, G.M. Sex differences in the biotransformation of 2-acetylaminofluorene in cultured rat hepatocytes. Cell Biol Toxicol 2, 271–281 (1986). https://doi.org/10.1007/BF00122695

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  • DOI: https://doi.org/10.1007/BF00122695

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