PLACENTAL EXPRESSION OF ARYLAMINE N-ACETYLTRANSFERASES - EVIDENCE FORLINKAGE DISEQUILIBRIUM BETWEEN NAT1-ASTERISK-10 AND NAT2-ASTERISK-4 ALLELES OF THE 2 HUMAN ARYLAMINE N-ACETYLTRANSFERASE LOCI NAT1 AND NAT2

The study of placental xenobiotic metabolism is important for the dete rmination of foetal exposure to environmental chemicals as placental m etabolism influences the nature of chemicals reaching the foetus from its mother's blood. Arylamine N-acetyltransferases are drug metabolizi ng enzymes which N-acetylate hydrazines and arylamines, including carc inogenic arylamines and sulphonamide drugs. The two human arylamine N- acetyltransferase isoenzymes, NAT1 and NAT2, are encoded at multi-alle lic loci. Here, we have determined N-acetyltransferase (NAT) activity in term placentas from normal, uncomplicated pregnancies. Both NAT1 an d NAT2 enzyme activities were detectable. Placental NAT1 activity was at least 1000 fold greater than NAT2 activity. There was a 6 fold inte r-placental variation in NAT1 activity. Mean placental NAT1 specific a ctivity was 1.42 nmoles para-aminobenzoic acid N-acetylated.min(-1).mg protein(-1), which is comparable to NAT1 specific activities which ha ve been measured in adult tissues. The NATL, but not the NAT2, protein was detectable in placentas by Western blotting. Maternal and foetal NAT genotypes were determined from placenta, using placental blood clo ts and cord blood respectively, allowing NAT haplotype determination. There appeared to be linkage disequilbrium between NAT1 and NAT2* all eles such that the combination NAT110/NAT2*4 was found 3.5 times more frequently than would be expected.