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-Acetyltra nsferases are known to metabolize aromatic amine bladder carcinogens, but the functional significance of NAT expression in the target organ is unclear, To resolve this issue, polyclonal antisera against purifie d recombinant enzymes and C-terminal peptides of human NAT Type 1 (NAT 1) and Type 2 (NAT2) were generated, Western blot analysis of exfoliat ed cells from human urine, pig bladder homogenate, and human bladder t umor-derived cell lines showed that NAT1 was expressed in all three sy stems, whereas NAT2 did not appear to be expressed in the bladder. Imm unohistochemical analysis of human bladder tumor sections indicated th at well-differentiated tumor cells expressed NAT1, with the highest le vel of expression being found in the umbrella cells that line the blad der lumen. Poorly differentiated tumor regions appeared to express NAT 1 at lower levels than did well-differentiated areas, These findings s upport the hypothesis that aromatic amines are metabolized in the blad der epithelium by NAT1.