EXTRAHEPATIC EXPRESSION OF N-ACETYLATOR GENOTYPE IN THE INBRED HAMSTER

  • 1 January 1987
    • journal article
    • research article
    • Vol. 15  (1) , 68-73
Abstract
The genetic control of S-acetylcoenzyme A (AcCoA)-dependent N-acetyltransferase activity (EC 2.3.1.5) was investigated in liver, intestine, kidney, and lung cytosols dervied from homozygous rapid acetylator (Bio. 87, 20), heterozygous acetylator (Bio. 87.20 .times. 82.73/HF1), and homozygous slow acetylator (Bio. 82.73/H) Syrian inbred hamster. AcCoA-dependent N-acetyltransferase activity as highest in hepatic cytosol, followed by intestine, kidney, and lung cytosol. In each of these tissues cytosolic N-acetyltransferase exhibited an acetylator genotype-dependent activity with highest levels in homozygous rapid, intermediate levels in heterozygous F1 progeny, and lowest levels in homozygous slow acetylators. The ratio of N-acetyltransferase activity between acetylator genotypes was in general substrate dependent but not tissue dependent. Acetylator genotype-dependent N-acetyltransferase activity differences were highest for p-aminobenzoic acid, followed by-aminosalicylic acid, 2-aminofluorene, and .beta.-naphthylamine. Expression of isoniazid N-acetyltransferase activity in each tissue was acetylator genotype independent. Determination of Michaelis-Menten kinetic constants in each tissue suggested that p-aminobenzoic acid N-acetyltransferase activity was acetylator genotype-dependent because of catalysis by an isozyme(s) that is both an apparent Km and a Vmax variant. In contrast, the acetylator genotype-independent expression of isoniazid N-acetyltransferase activity in each tissue appeared to result from a common isozyme(s) present in each tissue with equivalent kinetic constants in the two phenotypes. These data suggest that acetylator genotype-dependent expression of AcCoA-dependent N-acetyltransferase activity in extrahepatic tissues may play an important role in hereditary predisposition to toxicity and/or carcinogenesis in extrahepatic organs following exposure to arylamine drug and foreign chemicals.