ABSTRACT
The metabolism of N-2-fluorenylacetamide (FAA) and N-hydroxy-2-fluorenylacetamide (N-OH-FAA) was studied in groups of rats that had been prefed the protective agent p-hydroxyacetanilide (p-OH-AA) alone or in combination with each of the carcinogens for 4 weeks. Compared with controls, pretreatment increased the percentage of metabolites in the urine, chiefly as glucuronic acid conjugates, whereas the fecal excretion of FAA metabolites was lowered. The levels of total and tissue-bound material in the liver and blood plasma were also lower after prefeeding. Liver aryl hydrocarbon hydroxylase and liver deacetylase were not affected by p-OH-AA pretreatment. However, liver glucuronyl transferase was increased by either prefeeding with p-OH-AA and/or the carcinogen. The protective effect of p-OH-AA against liver tumor induction with FAA or N-OH-FAA may in part result from a combination of the decreased binding of carcinogen to hepatic cellular macromolecules and the increased excretion as the glucuronide conjugates.
Subject(s)
2-Acetylaminofluorene/antagonists & inhibitors , Acetaminophen/pharmacology , Fluorenes/antagonists & inhibitors , Hydroxyacetylaminofluorene/antagonists & inhibitors , 2-Acetylaminofluorene/metabolism , 2-Acetylaminofluorene/urine , Amidohydrolases/metabolism , Animals , Body Weight/drug effects , Eating , Feces/analysis , Glucuronates/metabolism , Glucuronosyltransferase/metabolism , Hydroxyacetylaminofluorene/metabolism , Hydroxyacetylaminofluorene/urine , Liver/enzymology , Liver/metabolism , Male , Protein Binding , Rats , Rats, Inbred F344 , Sulfuric Acids/metabolismABSTRACT
A comparative study of the metabolism of the carcinogen N-2-fluorenylacetamide by mice of the X/Gf strain (resistant to the tumorigenic action) and the NiH Swiss strain (susceptible to the tumorigenic action) showed slight but not outstanding differences in metabolic patterns. The activated metabolite N-hydroxy-N-2-fluorenylacetamide was excreted by both strains, and the levels of carcinogens or metabolites bound to liver macromolecular constituents were comparable in the X/Gf and NiH Swiss mice.
