Sex differences in the biotransformation of 2-acetylaminofluorene in cultured rat hepatocytes.
Sex-related differences in susceptibility 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 x 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.
McQueen
C A
CA
American Health Foundation, Valhalla, New York 10595.
Miller
M J
MJ
Williams
G M
GM
D015073:2-Acetylaminofluorene / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012727:Sex Characteristics
D015073:2-Acetylaminofluorene