Enzymatic deacetylation of N-hydroxy-2-acetylaminofluorene by liver microsomes.
نویسنده
چکیده
Af-Hydroxy-2-acetylaminofluorene was rapidly deacetylated by guinea pig liver and, to a lesser extent, by other guinea pig tissues examined. The enzyme activity was located in the microsomal fraction of the liver. The enzyme appeared to be stimulated by trisodium pentacyanoamine ferrate, and it was inhibited by SKF-525A (|3-diethylaminoethyldiphenylpropyl acetate hydrochloride), by sodium fluoride, and by diethyl p-nitrophenyl phosphate. The inhibition by diethyl p-nitrophenyl phosphate was complete at a concentration of 10~6M.Chloride or magnesium
منابع مشابه
Metabolism of /V-Hydroxy-2-acetylaminofluorene and A/-Hydroxy-2- aminofluorene by Guinea Pig Liver Microsomes1
The guinea pig is resistant to the hepatocarcinogenic effects of 2-acetylaminofluorene and 2-aminofluorene. This resist ance, however, is not due to the lack of a A/-hydroxylating enzyme in the liver which catalyzes the first and rate-limiting step to the activation of these chemicals to proximal carcino gens. It is shown that guinea pig liver microsomes can A/-hydroxylate both of these compoun...
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In 1960, Cramer, Miller, and Miller (1) reported the discovery of a new metabolite of the carcinogen 2-acetylaminofluorene, and from this discovery there has evolved a hypothesis concerning the mechanism of action of carcinogenic aromatic amines (2-5). This metabolite, N-hydrosy-2.acetylaminofluorene, has been found in the urine of animals fed 2-acetylaminofluorene only as a conjugate cleavable...
متن کاملEnzymatic N-hydroxylation of the Carcinogen 2-acetylaminofluorene and the Metabolism of N-hydroxy-2-acetylaminofluorene-9-14c in Vitro.
In 1960, Cramer, Miller, and Miller (1) reported the discovery of a new metabolite of the carcinogen 2-acetylaminofluorene, and from this discovery there has evolved a hypothesis concerning the mechanism of action of carcinogenic aromatic amines (2-5). This metabolite, N-hydrosy-2.acetylaminofluorene, has been found in the urine of animals fed 2-acetylaminofluorene only as a conjugate cleavable...
متن کاملMetabolism and activation of 2-acetylaminofluorene in isolated rat hepatocytes.
The metabolism of 2-acetylaminofluorene (AAF) as well as the activation of AAF to covalently bound and mutagenic intermediates were studied in isolated rat hepatocytes. The cell system readily formed oxidized, deacetylated, and conjugated AAF metabolites. Pretreatments of animals with the inducer beta-naphthoflavone led to increases in phenolic and conjugated as well as covalently protein-bound...
متن کاملThe enzymatic reduction of the N-hydroxy derivatives of 2-acetylaminofluorene and related carcinogens by tissue preparations.
cause the hydroxamic acid is readily reduced both in vivo and in vitro (9, 13, 16, 22), the balance of the N-hydroxyla tion and reduction reactions is of considerable importance in determining the carcinogenic dose applied to the tissues. Studies on the microsomal system which N-hydroxylates AAF have been reported by Irving (13) and are in progress in this laboratory (17). The present paper rep...
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ورودعنوان ژورنال:
- Cancer research
دوره 26 7 شماره
صفحات -
تاریخ انتشار 1966