1. ¹Department of Pediatrics, Colleges of Medicine and Pharmacy, University of Arizona, Tucson, AZ, USA
2. ²Department of Pharmacology and Toxicology, Colleges of Medicine and Pharmacy, University of Arizona, Tucson, AZ, USA
3. ³Department of Molecular and Cellular Biology, College of Science, University of Arizona, Tucson, AZ, USA

Correspondence: Dr RP Erickson, Department of Pediatrics, University of Arizona, 1501 N Campbell Avenue, 4341A/PO Box 245073, Tucson, AZ 85724-5073, USA. Tel: +1 520 626 5483; Fax: +1 520 626 7407; E-mail: erickson@peds.arizona.edu

⁴Current address: Department of Clinical Pharmacology, Jinling Hospital, 305 E Zhongshan Road, Nanjing, Jiangsu Province 210002, People's Republic of China

Received 22 December 2004; Revised 29 March 2005; Accepted 2 May 2005.

Abstract

Therapeutic and environmental aromatic amines and hydrazines are substrates for the arylamine N-acetyltransferases (NAT). In all, 10 transgenic lines containing either the human NAT1 or NAT2 transgene were developed using multiple promoters. The presence of the transgene was confirmed by determining copy number, mRNA and enzyme activity. Despite some lines having high copy numbers of the transgene, only modest or no increases in enzymatic activity could be found in a variety of tissues. The NAT1 transgene could not be bred to homozygosity. The cytomegalovirus (CMV)-promoted NAT1 transgene increased endogenous Nat1 mRNA levels in liver and had little effect on endogenous Nat2 mRNA levels. The presence of the CMV-promoted NAT2 transgene appeared to suppress endogenous hepatic Nat2 mRNA, but did not alter Nat1 mRNA levels. The failure to achieve high expression of any of the transgenes suggests that overexpression of NAT genes may have harmful effects during development.