Activation and detoxication of carcinogenic arylamines by sulfation

Hepatic sulfation of heterocyclic and non-heterocyclic arylamines was studied to assess enzymes responsible for their metabolisms. Both 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)- and non-IQ-type (beta-carboline) heterocyclic amines were N-sulfated to form their sulfamates in cytosols of rat livers in the presence of 3'-phosphoadenosine-5'-phosphosulfate (PAPS). An arylsulfo-transferase, ST1A1, whose cDNA was isolated from a rat cDNA library, was expressed in COS-1 cells. The expressed enzyme catalyzed N-sulfation of IQ, but not appreciably those of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-I), and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). N-Sulfation of heterocyclic amines except IQ was higher in hepatic cytosols of female rats than of male rats. These results suggest the involvement of at least plural forms of sulfotransferase on the N-sulfation. In addition, N-sulfation of IQ was also observed in cytosol of a human liver, suggesting that N-sulfation is one of the metabolic pathways of heterocyclic amines in humans as well as rats. Hepatic sulfotransferase also catalyzes metabolic activation of N-hydroxy derivatives of carcinogenic arylamines. Using anti-HAST (hydroxylarylamine sulfotransferase) antibodies and ST1A1 cDNA as screening probes, several cDNA clones were isolated from the cDNA library. A new member of arylsulfotransferase, ST1C1, whose cDNA shows considerable sequence similarity to ST1A1 cDNA, was found to catalyze O-sulfation of N-hydroxy-2-acetylaminofluorence by the cDNA expression in COS-1 cells. From the close similarity of ontogenic profile and sex-specific expression of ST1C1 and HAST, ST1C1 cDNA was shown to encode a major sulfotransferase (HAST) mediating the metabolic activation of N-hydroxyarylamines in rat livers. In addition, properties of PAPS-dependent N-hydroxyarylamine activation and sulfotransferase in human livers are also discussed.