Distribution of 2-aminofluorene and p-aminobenzoic acid N- acetyltransferase activity in tissues of C57BL/6J rapid and B6.A-NatS slow acetylator congenic mice.
Chung-JG; Levy-GN; Weber-WW
Drug Metab Dispos 1993 Nov; 21(6):1057-1063
Mouse tissues were tested to determine which contain measurable N- acetyltransferase (NAT) activity and to compare levels of activity between rapid and slow acetylator mice. The experiments used inbred C57BL/6J (B6)-mice and slow acetylator congenic B6.A-Nat(s)-mice. Tissue cytosols were incubated with either 2-aminofluorene (153786) or p-aminobenzoic-acid (150130). The tissues studied included samples taken from the gastrointestinal tract, lymphoid tissue, skin, blood components, and other major organs. With the exception of blood plasma and seminal vesicles, NAT activity was demonstrated in all tissues examined. The highest activity was observed in Peyer's patches with either substrate, and lymphoid tissue, in general, being high in NAT activity as was the skin and samples from the digestive system. In most tissues the acetylator polymorphism was apparent for both p-aminobenzoic-acid and 2-aminofluorene. With p-aminobenzoic-acid the difference between rapid and slow acetylator phenotypes was usually greater than with 2-aminofluorene. Immunoblots using an antiNAT antibody raised in rabbits demonstrated the presence of NAT in the 33 tissues of rapid and slow acetylator mice as well as the absence of NAT in plasma and seminal vesicles. The authors conclude that there is a widespread distribution of NAT activity and that a relative abundance of extrahepatic N-acetylation capacity exists in the mouse.
NIOSH-Publication; NIOSH-Grant; Cancer; Tissue-distribution; Gastrointestinal-system; Blood-analysis; Enzyme-activity; Carcinogens; Arylamines; Laboratory-animals
Pharmacology University of Michigan 6322 Medical Science I Bldg Ann Arbor, MI 48109-0626
Drug Metabolism and Disposition
University of Michigan at Ann Arbor, Ann Arbor, Michigan