title: Enzymatic acetylation and sulfation of N-hydroxyarylamines in bacteria and rat livers.
abstract: In mammalian hepatic cytosol both acetyltransferase and sulfotransferase are involved in the activation of N-hydroxy derivatives of arylamines and arylamides. The role of acetyltransferase is also shown in Salmonella, whereas no rigid evidence is provided on the role of sulfotransferase in Salmonella. In Ames mutagenesis test without S9-mix, the number of revertants of Salmonella typhimurium TA98 induced was 10-fold higher with 2-hydroxyamino-3-methylimidazo[4,5-f] quinoline (N-hydroxy-IQ) than with 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1). The extents of the binding to calf thymus DNA of N-hydroxy-Glu-P-1 were, however, 3.9 to 8.6-fold higher than that of N-hydroxy-IQ in both acetyl CoA- and PAPS-fortified rat hepatic cytosol systems. To understand the mechanism causing the apparent discrepancy between the results of the mutation and DNA binding, the activating capacities of cytosols of S. typhimurium TA98 and TA98/1,8-DNP6 strains on the binding of N-hydroxy-Glu-P-1 and N-hydroxy-IQ have been examined in comparison with those of rat livers. Although both N-hydroxyarylamines were activated by hepatic cytosols in the presence of PAPS, no significant DNA binding of these N-hydroxyarylamines was detected in the presence of PAPS and either one of the two strains of bacterial cytosols. In addition, both cytosols of TA98 and TA98/1,8-DNP6 strains showed no measurable activity on the sulfation of p-nitrophenol, suggesting no capacity for sulfotransferase-mediated activation of N-hydroxyarylamines in Salmonella. On the contrary, the extents of the acetyl CoA-dependent binding of N-hydroxy-IQ in cytosols of TA98, but not of TA98/1,8-DNP6, were respectively 6- and 9-fold higher than those in hepatic cytosols of male and female rats, although the extents of the binding of N-hydroxy-Glu-P-1 were rather higher in hepatic than in bacterial cytosols. In addition, the covalent binding of N-hydroxy-2-acetylaminofluorene to DNA was detected in hepatic, but not in bacterial cytosols, although the binding of N-hydroxy-2-aminofluorene was detectable in both hepatic and bacterial cytosols in the presence of acetyl CoA. These results indicate that the metabolic activating capacities of Salmonella and rat liver cytosols differ qualitatively, and the difference in the substrate specificity of acetyltransferase between Salmonella and rat livers may be involved, in part, in the difference of their DNA damage in bacteria and mammals.
authors.affiliation: Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamazoe
authors.forename: M
authors.initials: M
authors.lastname: Abu-Zeid
authors.forename: D W
authors.initials: DW
authors.lastname: Gong
authors.forename: N
authors.initials: N
authors.lastname: Staiano
authors.forename: R
authors.initials: R
authors.lastname: Kato
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism*; D000588:Amines / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D004247:DNA / Q000378:metabolism; D005260:Female; D006571:Heterocyclic Compounds / Q000378:metabolism* / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D009152:Mutagenicity Tests; D009154:Mutation; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000201:enzymology*; D015238:Sulfotransferases / Q000378:metabolism*
chemical_list: D000588:Amines; D006571:Heterocyclic Compounds; D004247:DNA; D000123:Acetyltransferases; D015238:Sulfotransferases