Studies on the Etiology of Bovine Bladder Cancer*

Bovine urinary bladder tumors, rarely seen in the United States, are more frequently found in certain other parts of the world.These tumors are commonly associated with a syndrome known as chronic enzootic hematuria,' which has been reported as occurring in certain portions of the Northwest coastal area of the United States2 and Canada: F o r m o ~a , ~ Turkey,6 and other areas of the world.The geographical distribution and the endemic nature of this disease are reminiscent of two similar outstanding features exhibited by industrial cancers of the bladder that occur in workmen exposed to various chemicals in their environment.However, in contradistinction to the industrial cancers of the bladder, where at least three aromatic amines have been implicated as causative factors, the etiology of the naturally occurring bovine urinary bladder tumors remains obscure.Numerous factors have been suggested as of possible etiologic significance, and the bracken fern, Pteris aquilina, has been frequently observed and associated with the occurrence of hematuria in ~a t t l e .~The pathological structure and clinical course of many spontaneous bladder tumors in cattle do not differ significantly from either the industrial bladder tumors seen in dye workers6 or from the spontaneous bladder tumors observed in other individuals.6It is attractive to hypothesize that similar, if not common, factors may be operative in the genesis of these materially similar neoplasms.Perhaps more is known and understood about the detailed chemical causation of human bladder cancer than is known for any other human tumor.Three primary aromatic amines, 2-naphthylamine, benzidine and Caminodiphenyl, have been implicated on the basis of good clinical and epidemiological data's" as being of causal significance in some human bladder cancers.Though it was first postulated by Rehng in 1895 that exposure of workmen to various chemicals in their environment incited the subsequent development of urinary bladder tumors, it was not until 1937 that this disease was first reproduced in experimental animals.Hueper and co-workers1° first reported that 2-naphthylamine when given orally in high doses to dogs induced tumors of the bladder which resembled the human disease in all respects.In a similar manner, benzidine" and 4-aminodiphenyl12 were subsequently shown to be capable of inducing bladder carcinoma in dogs.