Immunochemical detection of arylamine N-acetyltransferase in normal and neoplastic bladder.
The N-acetyltransferase (NAT) phenotype is an important determinant of individual susceptibility to occupational bladder cancer. N-Acetyltransferases arc known to metabolize aromatic amine bladder carcinogens, but the functional significance of NAT expression in the target organ is unclear. To resolve this issue, polygonal antisera against purified recombinant enzymes and C-terminal peptides of human NAT Type 1 (NAT1) and Type 2 (NAT2) were generated. Western blot analysis of exfoliated cells from human urine, pig bladder homogenate, and human bladder tumor-derived cell lines showed that NAT1 was expressed in all three systems, whereas NAT2 did not appear to be expressed in the bladder. Immunohistochemical analysis of human bladder tumor sections indicated that well-differentiated tumor cells expressed NAT1, with the highest level of expression being found in the umbrella cells that line the bladder lumen. Poorly differentiated tumor regions appeared to express NAT1 at lower levels than did well-differentiated areas. These findings support the hypothesis that aromatic amines are metabolized in the bladder epithelium by NAT1.
Stanley
L A
LA
Department of Pharmacology, University of Oxford, United Kingdom.
Coroneos
E
E
Cuff
R
R
Hickman
D
D
Ward
A
A
Sim
E
E
D000595:Amino Acid Sequence; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002273:Carcinogens / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D013552:Swine; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000166:cytology / Q000201:enzymology*; D001749:Urinary Bladder Neoplasms / Q000201:enzymology*
D014408:Biomarkers, Tumor; D002273:Carcinogens; D010446:Peptide Fragments; D011994:Recombinant Proteins; D001191:Arylamine N-Acetyltransferase