title: Further characterization of the ability of hepatocarcinogens to lower rat liver aryl sulfotransferase activity.
abstract: Aryl sulfotransferase (AST) activity in rat liver is thought to be a primary pathway in the bio-activation of various hepatocarcinogens to forms which act as ultimate carcinogens in chemical hepatocarcinogenesis. In an effort to understand the significance of rapid and sustained decreases in liver AST that accompany dietary administration of hepatocarcinogens and to further assess its relationship to carcinogenic processes, we determined the abilities of various xenobiotics known to be hepatocarcinogens or non-hepatic carcinogens to lower AST activity. We also determined whether the co-administration of the AST enzyme inhibitor, pentachlorophenol, with hepatocarcinogens will abrogate the lowering of AST activity caused by hepatocarcinogens which do not utilize AST for bio-activation versus hepatocarcinogens which can utilize AST. Among carcinogens tested thus far, we have found the AST activity of liver cytosols to be lowered by the hepatocarcinogens 2-acetylaminofluorene, ethionine, 3'-methyl-4-dimethylaminoazobenzene, thioacetamide, aflatoxin B1, diethylnitrosamine and benzidine, but not by the non-hepatic carcinogens 2-acetylaminophenanthrene or 3-methylcholanthrene. Pentachlorophenol reversed activity losses when co-administered with all carcinogens which lowers AST activity with the exception of ethionine and thioacetamide. We suggest that AST activity lowering is relatively specific for liver carcinogens and involves two different mechanisms.
mesh_terms: D000818:Animals; D015239:Arylsulfotransferase; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010416:Pentachlorophenol / Q000494:pharmacology; D051381:Rats; D013466:Sulfurtransferases / Q000037:antagonists & inhibitors*
chemical_list: D002273:Carcinogens; D010416:Pentachlorophenol; D013466:Sulfurtransferases; D015239:Arylsulfotransferase