Inheritance of acetylator genotype-dependent arylamine N-acetyltransferase in hamster bladder cytosol.
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 X Bio. 82.73/H F1 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 Km and Vmax 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.
D000107:Acetylation; D000123:Acetyltransferases / Q000032:analysis*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000032:analysis*; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology*; D005838:Genotype; D006720:Homozygote; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008647:Mesocricetus; D001743:Urinary Bladder / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase