Genetic regulation of aromatic amine N-acetylation in inbred mice.
A survey among 20 inbred mouse strains revealed large variation (up to approximately 20-fold) for the N-acetylation of p-aminobenzoic acid by blood N-acetyltransferase and for the aromatic amine carcinogen benzidine by both liver and blood N-acetyltransferase. Of 20 strains surveyed, three are classified as slow acetylators (A/J, AHe/J, and X/Gf) and 17 are classified as rapid acetylators (AuSsJ, Castaneous, ST/bJ, C57BL/6J, Molossinus, SF, SWR/J, 129/SV, RF/J, RIII/2J, IsCam, SJL/J, Balb/cJ, C3H/HeJ, CBA/J, AKR/J, and DBA/J). The rapid acetylator strains possessed approximately 10 times greater liver benzidine N-acetyltransferase specific activity than the slow acetylator strains. Intercross and backcross matings of A/J and C57BL/6J mice indicate that a single gene with two major alleles is responsible for differences in N-acetyltransferase activity in blood for p-aminobenzoic acid or the alternate aromatic amine carcinogen aminofluorene, and in liver for aminofluorene. Analysis of 11 recombinant inbred strains derived from matings of A/J with C57BL/6J mice support this conclusion and demonstrate the existence of minor modifying genes that segregate independently of the major N-acetyltransferase gene.
D010129:4-Aminobenzoic Acid / Q000097:blood / Q000378:metabolism; D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D003433:Crosses, Genetic; D014644:Genetic Variation; D008099:Liver / Q000201:enzymology; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D013045:Species Specificity; D013379:Substrate Specificity
D000123:Acetyltransferases; D010129:4-Aminobenzoic Acid