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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
Author(s) -
Hein David W.,
Doll Mark A.,
Nerland Donald E.,
Fretland Adrian J.
Publication year - 2006
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20164
Subject(s) - acetylation , n acetyltransferase , acetyltransferase , arylamine n acetyltransferase , hamster , biology , congenic , microbiology and biotechnology , enzyme , carcinogen , biochemistry , gene
Abstract 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 NAT 2 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 ( r 2 = 0.871; P < 0.0001) but not with NAT1 activities ( r 2 = 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 ( r 2 = 0.695; P < 0.0001) and NAT2 activities ( r 2 = 0.521, P < 0.0001) but not with NAT1 activities ( r 2 = 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. © 2006 Wiley‐Liss, Inc.