Rapid decrease in N-hydroxy-2-acetylaminofluorene sulfotransferase activity of liver cytosols from rats fed carcinogen

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