SULFATION OF N-HYDROXY-4-AMINOBIPHENYL AND N-HYDROXY-4-ACETYLAMINOBIPHENYL BY HUMAN FETAL AND NEONATAL SULFOTRANSFERASE

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 an d foetal and neonatal adrenal gland. Sulphotransferase (ST) activity c apable of sulphating these compounds was present in foetal liver and a drenal gland by 14 weeks of gestation. Sulphation of N-OH-4ABP was hig her 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 tha t towards 1-naphthol. In foetal and neonatal liver cytosol the sulphat ion of N-OH-4ABP was also higher than that of N-OH-4AABP (approximatel y 2-fold). In adult liver cytosols, however, N-OH-4AABP ST activity wa s higher than that for N-OH-4ABP and 1-naphthol sulphation. Aromatic h ydroxylamines and hydroxamic acids are known to be converted by sulpho transferase into reactive, electrophilic compounds capable of reacting with DNA. Our data show that the human foetus and neonate have the ca pacity to sulphate these compounds and thus is able to produce the rea ctive mutagenic metabolites. Therefore, this class of genotoxic compou nds may be bioactivated by humans during development-a time when they are most vulnerable to the effects of genotoxins.