Biochemical characterization of genetically variant aromatic amine N-acetyltransferases in A/J and C57BL/6J mice.

Biochemical genetic studies to determine the molecular basis for the differences in N-acetylation between the A/J and C57BL/6J mouse strains were carried out. Purification of liver N-acetyltransferase from both strains showed that aminofluorene and p-aminobenzoic acid activities are not separable by protein purification techniques which exploit differences in charge and size. In addition, both aminofluorene and p-aminobenzoic acid N-acetyltransferase activities from the C57BL/6J mouse liver enzymes migrated as a single symmetrical protein band after polyacrylamide disc gel electrophoresis. For aminofluorene and p-aminobenzoic acid, the two mouse strains showed apparent Km differences which suggest a difference in a structural gene product, and at least may partially account for the observed differences in N-acetylation. N-Acetyltransferase activity of selected extrahepatic tissues showed that both small intestine and kidney reflect the animal's phenotype as determined by liver or blood N-acetyltransferase. Sex differences were apparent in this activity in C57BL/6J mouse kidney, with males exhibiting approximately 2.5-fold higher activity for aminofluorene and approximately 3-fold higher activity for p-aminobenzoic acid than did females.