The Effects of Hepatotoxic Agents and of Liver Growth on the Urinary Excretion of the 7V-Hydroxy Metabolite of 2-Acetylaminofluorene by Rats*
نویسندگان
چکیده
Adult rats subjected to a number of treatments which cause liver damage and/or growth (administration of hepatotoxic agents, partial hepatectomy, or protein deple tion-repletion) and young growing rats excreted in the urine a greater percentage of a test dose of 2-acetylaminofluorene (AAF) as the carcinogenic Af-hydroxy metabolite than did normal adult rats. Alterations in the urinary excretion of the noncarcinogenic ring-hydroxy derivatives of AAF under these conditions were much smaller and, in most cases, negligible. Rats fed certain thermally oxidized derivatives of corn oil excreted 1^-2 times as much W-hydroxy-AAF in the urine after a test dose of AAF as rats fed fresh corn oil. These effects are correlated with the increased carcinogenicity of AAF when fed with the thermally oxidized products (Sugai et al.).
منابع مشابه
The Effects of Hepatotoxic Agents and of Liver Growth on the Urinary Excretion of the N-hydroxy Metabolite of 2-acetylaminofluorene by Rats.
Adult rats subjected to a number of treatments which cause liver damage and/or growth (administration of hepatotoxic agents, partial hepatectomy, or protein deple tion-repletion) and young growing rats excreted in the urine a greater percentage of a test dose of 2-acetylaminofluorene (AAF) as the carcinogenic Af-hydroxy metabolite than did normal adult rats. Alterations in the urinary excretion...
متن کاملEffect of glutathione depletion on the hepatotoxicity and covalent binding rat liver macromolecules of N-hydroxy-2-acetylaminofluorene.
Glutathione plays an important role in the protection of the liver against several hepatotoxins. The hepatocarcinogen N-hydroxy-2-acetylaminofluorene is converted in the rat in vivo to reactive metabolites that bind covalently to cellular macromolecules. These metabolites may also react with glutathione, resulting in the formation of glutathione conjugates and in the detoxification of reactive ...
متن کاملN-Hydroxylation: A new metabolic reaction observed in the rat with the carcinogen 2-acetylaminofluorene.
In their comprehensive work on 2acetylaminofluorenel (Fig. 1) the Weisburgers and Morris (l-4) have identified six phenolic metabolites of this carcinogen in the urine of adult rats. During recent studies (5) on this compound we have encountered a new acidic urinary metabolite. This metabolite is of interest since its excretion is greatly reduced by administration of a-methylcholanthrene, a pot...
متن کاملThe N- and Ring-Hydroxylation of 2-Acetylaminofluorene during Carcinogenesis in the Rat* JAMES
The new major metabolite of @-acetylaminofluorene (AAF) in the rat, N-hydroxy AAF, was excreted in the urine as a conjugate in amounts that increased during car cinogenesis; the amount at 18 weeks was about 9 times that at 1@weeks. When 3methylcholanthrene, which greatly inhibits the carcinogenicity of AM?, was fed with AAF, the excretion of N-hydroxy-AAF remained low, while the excretion of 3a...
متن کاملEffects of safrole and isosafrole pretreatment on N- and ring-hydroxylation of 2-acetamidofluorene by the rat and hamster.
1. The effects of safrole and isosafrole pretreatment on both N- and ring-hydroxylation of 2-acetamidofluorene were studied in male rats and hamsters. 2. Isosafrole (100mg/day per kg body wt.) pretreatment of rats for 3 days did not have any effect on urinary excretion of hydroxy metabolites of 2-acetamidofluorene. However, similar pretreatment with safrole produced increased urinary excretion ...
متن کامل