Sulphation of N-hydroxy-4-aminobiphenyl and N-hydroxy-4-acetylaminobiphenyl by human foetal and neonatal sulphotransferase.
Sulphation of the genotoxic compounds N-hydroxy-4-aminobiphenyl (N-OH-4ABP) and N-hydroxy-4-acetylaminobiphenyl (N-OH-4AABP) was determined in cytosolic preparations of human foetal, neonatal and adult liver and foetal and neonatal adrenal gland. Sulphotransferase (ST) activity capable of sulphating these compounds was present in foetal liver and adrenal gland by 14 weeks of gestation. Sulphation of N-OH-4ABP was higher in foetal and neonatal adrenal cytosol than was sulphation of N-OH-4AABP and in general, N-OH-4ABP ST activity was also greater than that towards 1-naphthol. In foetal and neonatal liver cytosol the sulphation of N-OH-4ABP was also higher than that of N-OH-4AABP (approximately 2-fold). In adult liver cytosols, however, N-OH-4AABP ST activity was higher than that for N-OH-4ABP and 1-naphthol sulphation. Aromatic hydroxylamines and hydroxamic acids are known to be converted by sulphotransferase into reactive, electrophilic compounds capable of reacting with DNA. Our data show that the human foetus and neonate have the capacity to sulphate these compounds and thus is able to produce the reactive mutagenic metabolites. Therefore, this class of genotoxic compounds may be bioactivated by humans during development--a time when they are most vulnerable to the effects of genotoxins.
Gilissen
R A
RA
Leiden/Amsterdam Center for Drug Research Division of Toxicology, University of Leiden, The Netherlands.
Hume
R
R
Meerman
J H
JH
Coughtrie
M W
MW
D000311:Adrenal Glands / Q000201:enzymology; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism*; D002458:Cell Fractionation; D003600:Cytosol / Q000201:enzymology; D005333:Fetus / Q000201:enzymology; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D008099:Liver / Q000201:enzymology; D015238:Sulfotransferases / Q000378:metabolism*
D000611:Aminobiphenyl Compounds; D002273:Carcinogens; C001365:N-hydroxy-4-acetylaminobiphenyl; C014593:N-hydroxy-4-aminobiphenyl; D015238:Sulfotransferases