Correlation between N-acetyltransferase activities in uroepithelia and in vivo acetylator phenotype.
The relationship between in vivo acetylator phenotype of individuals and N-acetyltransferase (NAT) activity in the cytosol of their cultured uroepithelia was examined in four urology patients. In vivo acetylator phenotypes were assigned by determining the ratio of N-acetyl vs. total [N-acetyl+free] sulfamethazine in urine and blood following a single oral dose (1 gm) of sulfamethazine. From the same patients, a surgical specimen of the ureter was obtained, uroepithelial cells were cultured in vitro, and the cytosols prepared. NAT activities were determined by measuring the amount of 4-acetylaminobiphenyl formed from incubation of uroepithelial cytosol with the substrate, 4-aminobiphenyl, and the cofactor [14C]acetyl coenzyme A. The two individuals phenotyped as "slow acetylators" by the in vivo method had NAT activities of 8.3 and 16.2 pmol 4-acetylaminobiphenyl/mg protein/min. In contrast, the two individuals phenotyped as "rapid acetylators" showed activities of 50.9 and 109.5 pmol 4-acetylaminobiphenyl/mg protein/min. The rapid acetylators exhibit about 6-fold greater uroepithelial NAT activities than slow acetylators, thus showing a direct correlation between the NAT activity in the uroepithelium, the target tissue of the human bladder carcinogen 4-aminobiphenyl, and the in vivo acetylator phenotype. These results imply that susceptibility of individuals to arylamine-induced bladder cancer might be associated with NAT activities in their target cells and that in vivo acetylator phenotyping could serve as a useful and relevant biochemical screening marker to assess the risk of developing bladder cancer.
Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison.
J C
JC
Pink
E M
EM
Messing
C A
CA
Reznikoff
G T
GT
Bryan
S
S
Swaminathan
D000107:Acetylation; D000123:Acetyltransferases / Q000032:analysis*; D000328:Adult; D000611:Aminobiphenyl Compounds / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D001743:Urinary Bladder / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000209:etiology
D000611:Aminobiphenyl Compounds; C006757:4-biphenylamine; D000123:Acetyltransferases