ACETYLATION OF ARYLAMINES BY THE PLACENTA

The N-acetylation of arylamines and hydrazines used as drugs may alter their pharmacological or toxicological activity. Arylamine N-acetyltr ansferases (NATs) are involved in drug metabolism, as they catalyse th e N-acetylation of arylamine and mono-substituted hydrazine substrates . Placental metabolism regulates the nature of the chemicals which rea ch the developing fetus. The study of drug metabolism during pregnancy is important in determining the effect on the fetus of drugs administ ered to the mother and the maternal drug dose required, important if t he treatment is to be effective. There are two forms of NAT in humans, NAT1 and NAT2, which are encoded at multi-allelic loci. There is inte r-individual variation in both NAT1 and NAT2 activity, which has impli cations in drug dosage. Using a combination of enzyme activity measure ments and Western blotting, this study has characterised the arylamine N-acetylation capabilities of placenta and cord blood. NAT1 activity in placenta and cord blood demonstrated inter-individual variation and the variation was in the range expected for adult NAT1 activity. The genotypes of both NAT1 and NAT2* were determined using DNA prepared u sing placental blood clots (maternal DNA) and cord blood (fetal DNA). The results indicate that placental NAT activity is an important facto r when considering N-acetylation during pregnancy.