Inheritance of acetylator genotype-dependent arylamine N-acetyltransferase in hamster bladder cytosol

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Abstract
Acetyl coenzyme A-dependent arylamine N -acetyltransferase (EC 2.3.1.5) was examined in bladder cytosol derived from inbred Syrian hamsters. Expression of N -acetyltransferase activity towards p -aminobenzoic acid, p -aminosalicylic acid and 2-aminofluorene was acetylator genotype-dependent. Highest levels of bladder N -acetyltransferase activity were expressed in homozygous rapid acetylator hamsters (Bio. 87.20), lowest levels in homozygous slow acetylator hamsters (Bio. 82.73/H), and intermediate levels in Bio. 87.20 × Bio. 82.73/H F 1 , generation progeny. The N -acetyltransferase activity was acetylator genotype-dependent in both epithelial and non-epithelial bladder tissue. Genetic crosses using p -aminobenzoic acid and p -aminosalicylic acid as substrates indicated that bladder N -acetyltransferase activity is controlled via simple autosomal Mendelian inheritance of two codominant alleles at a single genetic locus. Acetylator genotype as assessed by bladder N -acetyltransferase activity was completely concordant with acetylator genotype as assessed by liver N -acetyltransferase activity. N -Acetyltransferase in slow acetylator bladder cytosol was both an apparent K m and V max variant compared to N -acetyltransferase in rapid acetylator bladder cytosol. These results suggest that genetic control of arylamine N -acetyltransferase in bladder urothelium may be a factor in hereditary predisposition to arylamine-induced bladder cancer.