Tissue distribution of N-acetyltransferase 1 and 2 catalyzing the N-acetylation of 4-aminobiphenyl and O-acetylation of N-hydroxy-4-aminobiphenyl in the congenic rapid and slow acetylator Syrian hamster.
N-acetyltransferase 1 (NAT1) and 2 (NAT2) enzymes catalyzing both deactivation (N-acetylation) and activation (O-acetylation) of arylamine carcinogens such as 4-aminobiphenyl (ABP) were investigated in a Syrian hamster model congenic at the NAT2 locus. NAT2 catalytic activities (measured with p-aminobenzoic acid) were significantly (P < 0.001) higher in rapid than slow acetylators in all tissues (except heart and prostate where activity was undetectable in slow acetylators). NAT1 catalytic activities (measured with sulfamethazine) were low but detectable in most tissues tested and did not differ significantly between rapid and slow acetylators. ABP N-acetyltransferase activity was detected in all tissues of rapid acetylators but was below the limit of detection in all tissues of slow acetylators except liver where it was about 15-fold lower than rapid acetylators. ABP N-acetyltransferase activities correlated with NAT2 activities (r2 = 0.871; P < 0.0001) but not with NAT1 activities (r2 = 0.132; P > 0.05). Levels of N-hydroxy-ABP O-acetyltransferase activities were significantly (P < 0.05) higher in rapid than slow acetylator cytosols for many but not all tissues. The N-hydroxy-ABP O-acetyltransferase activities correlated with ABP N-acetyltransferase activities (r2 = 0.695; P < 0.0001) and NAT2 activities (r2 = 0.521, P < 0.0001) but not with NAT1 activities (r2 = 0.115; P > 0.05). The results suggest widespread tissue distribution of both NAT1 and NAT2, which catalyzes both N- and O-acetylation. These conclusions are important for interpretation of molecular epidemiological investigations into the role of N-acetyltransferase polymorphisms in various diseases including cancer.
Hein
David W
DW
Department of Pharmacology & Toxicology and James Graham Brown Cancer Center, The University of Louisville School of Medicine, Louisville, Kentucky 40292, USA.
Doll
Mark A
MA
Nerland
Donald E
DE
Fretland
Adrian J
AJ
D000107:Acetylation; D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000378:metabolism*; D002384:Catalysis; D002460:Cell Line; D006224:Cricetinae; D003600:Cytosol / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus / Q000378:metabolism*; D014018:Tissue Distribution
D000611:Aminobiphenyl Compounds; D007527:Isoenzymes; C006757:4-biphenylamine; C014593:N-hydroxy-4-aminobiphenyl; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human