Rodent models of the human isoniazid-acetylator polymorphism.
Inbred strains and subpopulations of rats, laboratory mice, and deer mice were examined for individual variation in the ability to metabolize several arylamines (p-aminobenzoic acid, sulfamethazine, aniline, alpha-naphthylamine, and aminofluorene) by N-acetylation. Individual differences within species were found to be dependent upon the tissue source of N-acetyltransferase activity and the acetyl acceptor employed. Long-Evans rats possessed about 2-fold more p-aminobenzoic acid N-acetyltransferase activity in blood and liver than Sprague-Dawley rats; no strain differences could be found with sulfamethazine. Nine strains of laboratory mice (Mus musculus) were found to have considerable liver p-aminobenzoic acid N-acetyltransferase activity but only slight activity towards sulfamethazine. No strain differences were apparent in regard to liver N-acetyltransferase activity. Blood p-aminobenzoic acid N-acetyltransferase activity was distinctly polymorphic in laboratory mice; of the nine strains tested, only A/J mice did not have this activity. Partially inbred deer mice (Peromyscus maniculatus) showed a narrower phenotypic range than random-bred stock from which they were obtained, which suggests the existence of distinct subpopulations with respect to N-acetylation capacity. Presumptive evidence for multiple forms of N-acetyltransferase in liver and blood was obtained through a study of substrate specificity.
D000107:Acetylation; D000818:Animals; D007538:Isoniazid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008805:Mice, Inbred A / Q000378:metabolism; D008807:Mice, Inbred BALB C / Q000378:metabolism; D008810:Mice, Inbred C57BL / Q000378:metabolism; D008811:Mice, Inbred DBA / Q000378:metabolism; D008954:Models, Biological; D010542:Peromyscus / Q000378:metabolism; D010641:Phenotype; D051381:Rats / Q000378:metabolism; D012377:Rodentia / Q000378:metabolism*; D013045:Species Specificity
D007538:Isoniazid