Sulfotransferase-mediated DNA binding of N-hydroxyarylamines(amide) in liver cytosols from human and experimental animals.
Characteristics of cytosolic sulfotransferase-mediated binding of carcinogenic N-hydroxyarylamines(amide) have been investigated and compared among experimental animal species and humans in vitro. Human cytosols exhibited significant sulfating activities towards 2-hydroxyamino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (N-hydroxy-Glu-P-1), N-hydroxy-2-aminofluorene (N-hydroxy-AAF) and N-hydroxy-2-acetylaminofluorene (N-hydroxy-AAF), but had no detectable activity toward 2-hydroxyamino-3-methyl-imidazo[4,5-f]quinoline (N-hydroxy-IQ). Although the extent of the covalent binding of these N-hydroxyarylamines(amide) differed significantly among individuals, clear correlations were observed among the sulfation of N-hydroxyarylamines (amide) and also with p-nitrophenol sulfation. Hepatic cytosols from mouse, rat, guinea-pig, hamster, rabbit, dog and monkey also mediated the binding of N-hydroxy-Glu-P-1, N-hydroxy-AF and N-hydroxy-AAF, while only rat cytosols showed detectable DNA binding of N-hydroxy-IQ. Among the species examined, rat showed the highest capability for activating these N-hydroxyarylamines(amides). Significant sex-related differences were detected in rat, dog and monkey for all substrates examined, except N-hydroxy-IQ. Clear correlations were observed in the animal species between N-hydroxyarylamines(amide), but not with p-nitrophenol. Using an ion-exchange chromatographic system, sulfating activity of p-nitrophenol in human livers was separated into two fractions and the PAPS-dependent DNA binding of N-hydroxy-AF was supported mainly by the later fraction. On Western blots, an immunoreactive protein was detected in these fractions using an antibody raised against rat hepatic N-hydroxy-AAF sulfotransferase. The band was also detected in human hepatic cytosols with considerable individual variation in their amounts. These results indicate the involvement of a closely related form(s) of sulfotransferase in the PAPS-mediated activation of N-hydroxyarylamines(amide) in human as well as in the experimental animal species.
Abu-Zeid
M
M
Department of Pharmacology, School of Medicine, Keio University, Tokyo, Japan.
Yamazoe
Y
Y
Kato
R
R
D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange; D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005449:Fluorenes / Q000378:metabolism; D006168:Guinea Pigs; D000882:Haplorhini; D006801:Humans; D006898:Hydroxylamines / Q000378:metabolism*; D007093:Imidazoles / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D009153:Mutagens / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000494:pharmacology; D011804:Quinolines / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012737:Sex Factors; D013045:Species Specificity; D015238:Sulfotransferases / Q000378:metabolism*
D005449:Fluorenes; D006898:Hydroxylamines; D007093:Imidazoles; D009153:Mutagens; D011804:Quinolines; D010724:Phosphoadenosine Phosphosulfate; C001368:N-hydroxy-2-aminofluorene; C023786:2-hydroxyamino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C032012:2-hydroxyamino-3-methylimidazolo(4,5-f)quinoline; D004247:DNA; D015238:Sulfotransferases