PT  - JOURNAL ARTICLE
AU  - J C Pink
AU  - E M Messing
AU  - C A Reznikoff
AU  - G T Bryan
AU  - S Swaminathan
TI  - Correlation between N-acetyltransferase activities in uroepithelia and in vivo acetylator phenotype.
DP  - 1992 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 559--565
VI  - 20
IP  - 4
4099  - http://dmd.aspetjournals.org/content/20/4/559.short
4100  - http://dmd.aspetjournals.org/content/20/4/559.full
SO  - Drug Metab Dispos1992 Jul 01; 20
AB  - 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.