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Toxicological Sciences 54, 19-29 (2000)
Copyright © 2000 by the Society of Toxicology

Localization of N-Acetyltransferases NAT1 and NAT2 in Human Tissues

Kelly F. Windmill*, Andrea Gaedigk{dagger},1, Pauline de la M. Hall{ddagger}, Hema Samaratunga§, Denis M. Grant{dagger} and Michael E. McManus*,2

* Department of Physiology and Pharmacology, University of Queensland, Queensland 4072, Australia; {dagger} Division of Clinical Pharmacology and Toxicology, Research Institute, The Hospital for Sick Children, Toronto, Canada M5G 1X8; {ddagger} Department of Histopathology, Flinders University of South Australia, SA, 5042 Australia; and § Pathology Department, Royal Brisbane Hospital, Queensland 4006, Australia

Human acetyl coenzyme A-dependent N-acetyltransferase (EC 2.3.1.5) (NAT) catalyzes the biotransformation of a number of arylamine and hydrazine compounds. NAT isozymes are encoded at 2 loci; one encodes NAT1, formerly known as the monomorphic form of the enzyme, while the other encodes the polymorphic NAT2, which is responsible for individual differences in the ability to acetylate certain compounds. Human epidemiological studies have suggested an association between the "acetylator phenotype" and particular cancers such as those of the bladder and colon. In the present study, NAT1- and NAT2-specific riboprobes were used in hybridization histochemistry studies to localize NAT1 and NAT2 mRNA sequences in formalin-fixed, paraffin-embedded human tissue sections. Expression of both NAT1 and NAT2 mRNA was observed in liver, gastrointestinal tract tissues (esophagus, stomach, small intestine, and colon), ureter, bladder, and lung. In extrahepatic tissues, NAT1 and NAT2 mRNA expression was localized to intestinal epithelial cells, urothelial cells, and the epithelial cells of the respiratory bronchioles. The observed heterogeneity of NAT1 and NAT2 mRNA expression between human tissue types may be of significance in assessing their contribution to known organ-specific toxicities of various arylamine drugs and carcinogens.

Key Words: N-acetyltransferase; carcinogenesis; hybridization histochemistry; liver; bladder..


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