Abstract
Our laboratory recently reported the successful construction of homozygous rapid (Bio. 82.73/H-Pat r) and homozygous slow (Bio. 82.73/H-Pat s) acetylator congenic Syrian hamsters. These hamsters are isogenic except for the polymorphic acetylator gene locus (Pat) and perhaps other closely linked loci. The purpose of the present investigation was to assess the expression of acetylator genotype both in vivo and in vitro in a variety of hepatic and extrahepatic organ cytosols. Levels of arylamine N-acetyltransferase were generally high and in the relative order: liver > colon > kidney > pancreas > prostate, urinary bladder, and lung. However, an acetylator gene dose-response was clearly expressed in each tissue, with highest levels in homozygousPat r acetylators, intermediate levels in heterozygousPat r/Pat s acetylators, and lowest levels in homozygousPat s acetylators. The magnitude of the acetylator genotype-dependent differences in N-acetyltransferase activity were substrate specific, whereinp-aminobenzoic acid showed the largest differences andp-aminophenol the smallest. The N-acetylation ofp-aminobenzoic acid in vivo also reflected acetylator genotype in the congenic hamsters. These results further document the successful construction of rapid and slow acetylator congenic hamsters which should prove very valuable in future studies to assess the role of acetylator genotype in the toxicity and carcinogenicity of arylamine chemicals.
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Hein, D.W., Rustan, T.D., Martin, W.J. et al. Acetylator genotype-dependent N-acetylation of arylamines in vivo and in vitro by hepatic and extrahepatic organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus. Arch Toxicol 66, 112–117 (1992). https://doi.org/10.1007/BF02342504
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DOI: https://doi.org/10.1007/BF02342504