Identification and inheritance of inbred hamster N-acetyltransferase isozymes in peripheral blood

Acetyl CoA-dependent p-aminobenzoic acid and p-aminosalicylic acid N-acetyltransferase (NAT) activity was determined in peripheral blood and blood cells from homozygous rapid (RR) acetylator (Bio. 87.20) and homozygous slow (rr) acetylator (Bio. 82.73/H) inbred hamsters and in their F1, F2 and backcross progeny. NAT activity was localized primarily in erythrocytes and was acetylator genotype dependent, as highest levels were expressed in homozygous rapid acetylator hamsters, intermediate levels in heterozygous acetylator hamsters and lowest levels in homozygous slow acetylator hamsters. Bio. 87.20 X Bio. 82.73/H F1 progeny expressed a unimodal nonoverlapping distribution of NAT activity intermediate between the RR and rr parentals. F2 generation progeny segregated into three modes (low, intermediate and high) of 21, 42 and 11, which is not significantly different from 1, 2 and 1. Bio. 82.73/H X F1 backcross progeny segregated into two modes (low and intermediate) of 18 and 16, whereas Bio. 87.20 X F1 backcross progeny segregated into two modes (intermediate and high) of 17 and 14, neither of which is significantly different from 1 and 1. These data are consistent with simple autosomal Mendelian inheritance of blood NAT activity by two codominant alleles at a single genetic locus. Partial purification of peripheral blood NAT activity by ion-exchange chromatography yielded separation of two isozymes that both exhibited acetylator genotype-dependent expression with highest activity in RR, intermediate activity in Rr and nondetectable activity in rr genotypes, respectively.