Expression of arylamine N-acetyltransferases in pre-term placentas and in human pre-implantation embryos.

Abstract

Arylamine N -acetyltransferases (NATs) catalyse the acetylation from acetyl-CoA of arylamines and hydrazines. There are two human isoenzymes which show polymorphism, and both enzymes are involved in the activation and detoxification of environmental carcinogens and teratogens. The two human isoenzymes NAT1 and NAT2 show different tissue distribution, with human NAT2 being found in liver and intestine whilst human NAT1 is expressed in many tissues including erythrocytes, bladder, lymphocytes and neural tissue, as well as liver and intestine. It has been proposed that NAT1 has an endogenous role in the acetylation of the folate catabolite p -aminobenzoyl-L-glutamate (pABGlu) to produce the major urinary product, N -acetyl-pABGlu. The murine homologue of human NAT1 is known to be concentrated in the neural tube during development. We show here that human NAT1 but not human NAT2 is expressed in pre-implantation embryos at the blastocyst stage and show that NAT1 is also expressed in early human placenta at the earliest available stage, 5.5 weeks. We demonstrate that there is inter-individual variation in NAT1 expression. In view of the role of folate in protecting against neural tube defects, we propose that NAT1 is a candidate risk factor for susceptibility to neural tube defects.