Polymorphic N-acetylation of sulfamethazine and benzidine by human liver: implication for cancer risk?
Extensive epidemiologic studies have indicated a relationship between bladder cancer in populations exposed to arylamines and the slow phenotype for acetylation of arylamines (e.g., sulfamethazine) and aryl hydrazides (e.g., isoniazid). In human liver preparations, we have examined the association between the capability for sulfamethazine acetylation and that for the human bladder arylamine carcinogen, benzidine. By the usual criteria for polymorphic acetylation, we classified the 10 donor subjects as four rapid and six slow acetylators of sulfamethazine. Concurrent tests of benzidine acetylation in the same liver preparations yielded capacities to acetylate benzidine that were directly and significantly correlated with those for sulfamethazine acetylation (r = 0.672; P less than 0.05). We suggest that acetylation of these two compounds is directly related and knowledge of the human acetylator phenotype may be a useful indicator of possible risk for bladder cancer due to exposure of certain arylamines and, perhaps for other cancers in man.
Peters
J H
JH
Life Sciences Division, SRI International, Menlo Park, CA 94025.
Gordon
G R
GR
Lin
E
E
Green
C E
CE
Tyson
C A
CA
D000107:Acetylation; D000293:Adolescent; D000328:Adult; D001560:Benzidines / Q000378:metabolism*; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012306:Risk; D013418:Sulfamethazine / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D001560:Benzidines; C029876:benzidine; D013418:Sulfamethazine