Mechanisms of the inhibitory action of p-hydroxyacetanilide on carcinogenesis by N-2-fluorenylacetamide or N-hydroxy-N-2-fluorenylacetamide.
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.
D015073:2-Acetylaminofluorene / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000652:urine; D000082:Acetaminophen / Q000494:pharmacology*; D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004435:Eating; D005243:Feces / Q000032:analysis; D005449:Fluorenes / Q000037:antagonists & inhibitors*; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006881:Hydroxyacetylaminofluorene / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000652:urine; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D013464:Sulfuric Acids / Q000378:metabolism
D005449:Fluorenes; D005965:Glucuronates; D013464:Sulfuric Acids; D000082:Acetaminophen; D006881:Hydroxyacetylaminofluorene; D015073:2-Acetylaminofluorene; D014453:Glucuronosyltransferase; D000581:Amidohydrolases