Sex differences in the biotransformation of 2-acetylaminofluorene in cultured rat hepatocytes |
| |
Authors: | Charlene A McQueen Mary Jo Miller Gary M Williams |
| |
Institution: | (1) American Health Foundation, Valhalla, New York;(2) American Health Foundation, 1 Dana Road, 10595 Valhalla, New York |
| |
Abstract: | 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.Abbreviations 2-AAF
2-acetylaminofluorene
- 2AF
2-aminofluorene
- WME
Williams Medium E. |
| |
Keywords: | 2-Acetylaminofluorene biotransformation hepatocytes sex differences |
本文献已被 SpringerLink 等数据库收录! |
|