The lower urinary tract of experimental animals has been actively studied since the search began for etiological factors in bladder carcinogenesis following the report in 1895 by Rehn that workers in the German aniline dye industry developed bladder cancer. The induction of bladder cancer in dogs by 2-naphthylamine, reported by Hueper and colleagues in 1938, established the experimental basis of bladder carcinogenesis. Induction in rodents was first observed following the oral administration of 2-acetylaminofluorene (AAF) to rats in 1941. Although of considerable usefulness in experimental bladder carcinogenesis research, AAF is a pluripotent carcinogen, inducing tumors of several tissues in addition to the urinary bladder, particularly the liver, breast, and ear duct. 1, 2 In the 1960s and early 1970s, organ-specific, chemically defined bladder carcinogens were discovered for rodents, including N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) administered in the drinking water, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) administered in the diet, and N-methyl-N-nitrosourea (MNU) instilled directly into the bladder lumen. These chemicals and their application provided the readily available, reproducible models necessary for detailed studies of the biochemical, pathobiological, and immunological mechanisms involved in the etiology and pathogenesis of bladder cancer.
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