Sulfation of carcinogenic aromatic hydroxylamines and hydroxamic acids by rat and human sulfotransferases: substrate specificity, developmental aspects and sex differences.
Sulfation of the carcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and structurally related hydroxamic acids by rat and human sulfotransferases was studied. There was a clear sex and age difference in the sulfation of N-OH-AAF and the other hydroxamic acids by rat liver cytosols; adult male rats had the highest sulfation activity. Experiments with purified aryl sulfotransferase IV (AST IV) indicated that the high expression of this enzyme in male rat liver may be responsible for these differences. No such sex or age difference was found for the sulfation of aromatic hydroxylamines. In cytosols of adult human livers, sulfation activity towards aromatic hydroxamic acids and hydroxylamines was clearly present, but activities were much lower than in rat liver cytosols. Sulfation activity towards these compounds was also found in fetal and neonatal liver and adrenals. These compounds probably are sulfated by several different sulfotransferases in humans.
LACDR-Center for Bio-Pharmaceutical Sciences, Division of Toxicology, Leiden University, The Netherlands.
J H
JH
Meerman
D P
DP
Ringer
M W
MW
Coughtrie
K J
KJ
Bamforth
R A
RA
Gilissen
D000375:Aging / Q000378:metabolism; D000818:Animals; D015239:Arylsulfotransferase / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology; D005260:Female; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism*; D006881:Hydroxyacetylaminofluorene / Q000378:metabolism; D006898:Hydroxylamines / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics; D013379:Substrate Specificity; D015238:Sulfotransferases / Q000378:metabolism*
D006877:Hydroxamic Acids; D006898:Hydroxylamines; D006881:Hydroxyacetylaminofluorene; C021378:N-hydroxy-2-acetylaminofluorene sulfotransferase; D015238:Sulfotransferases; D015239:Arylsulfotransferase