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- W2034220706 abstract "Abstract Sulfation of N -hydroxy-2-acetylaminofluorene ( N -OH-AAF) by N -OH-AAF sulfotransferase yields a candidate for ultimate carcinogen in hepatocarcinogenesis in rats. We have monitored this pathway during the initial phase(s) of hepatocarcinogenesis produced by feeding male Holtzman rats a diet containing 0.05% 2-acetylaminofluorene (AAF). Our studies revealed an immediate and precipitous decrease in N -OH-AAF sulfotransferase activity beginning after 1 day on the AAF diet and decreasing 4- to 5-fold after 5 days on the AAF diet. This decrease in activity remained at low values during continuous administration of AAF throughout 4 weeks but was shown to be both reversible and AAF dose dependent. Parallel monitoring of rat serum glutamic oxaloacetic acid transaminase activity during the administration of AAF indicated that no appreciable hepatocellular toxicity occurred during the period of sulfotransferase activity lowering. Other known carcinogenes, i.e. 3′-methyl- and 4′-fluoro-4-dimethylaminoazobenzene, aflatoxin B 1 , thioacetamide, ethionine, and diethylnitrosamine, and the hepatotoxin α-naphthylisothiocyanate, also caused decreases in N -OH-AAF sulfotransferase activity after 7 and 28 days of administration. In contrast, very weak or non-carcinogens, i.e. p -aminoazobenzene, fluorene, and barbital, failed to reduce N -OH-AAF sulfotransferase activity during 28 days of feeding. Data from these studies on the short-term chronic administration of xenobiotics suggest (a) reduced likelihood for the direct involvement of the sulfotransferase pathway in providing sufficient cytotoxic AAF metabolites to cause compensatory hyperplasia and its putative promotion-effect for AAF-mediated carcinogenesis, and (b) the possible use of the rapid loss in sulfotransferase activity as an early indicator of hepatocarcinogenesis." @default.
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- W2034220706 date "1983-01-01" @default.
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- W2034220706 title "Rapid decrease in N-hydroxy-2-acetylaminofluorene sulfotransferase activity of liver cytosols from rats fed carcinogen" @default.
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- W2034220706 doi "https://doi.org/10.1016/0006-2952(83)90561-0" @default.
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