The bladder cancer syndrome that often accompanies chronic enzootic hematuria in cattle grazing on pastures infested by bracken fern has been experimentally reproduced in animals fed a diet of bracken. The experimentally induced tumors were histologically and pathologically indistinguishable from the naturally occurring ones and comprised two main types: (a) carcinoma of the urothelium identical to that seen in humans; and (b) hemangioendotheliomas of the subjacent capillaries. Often the two types of tumor occurred together in the same bladder. In animals experimentally immunosuppressed with azathioprine “bracken type” hemangiomas developed in the bladder lining. DNA of bovine papillomavirus (BPV) type 2 was found in 46% (7 of 15) of the natural cancer cases and in 69% (9 of 13) of the experimentally induced lesions, independently of histological type and including the hemangiomas of the azathioprine-treated animals, suggesting a close association between BPV and bovine bladder neoplasia. Moreover, BPV-2 DNA was found in experimental animals that had not been inoculated with BPV at all or had been inoculated with a different BPV type and had been kept in isolation, suggesting that BPV can persist in a latent state and be activated when the animal is exposed to the bracken cocarcinogens and to immunosuppressants.

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