EXPERIMENTAL REPRODUCTION OF THE PAPILLOMA-CARCINOMA COMPLEX OF THE ALIMENTARY CANAL IN CATTLE

Bovine papillomavirus type 4 (BPV-4) is the aetiological agent of epit helial papillomas of the upper alimentary canal in cattle. These benig n tumours can become a focus for transformation to squamous cell carci nomas in animals feeding on bracken fern. Strong epidemiological evide nce suggests that the progression to malignancy is due to the interpla y between BPV-4 and mutagenic and immuno-suppressing chemicals present in the fern. The carcinomas of the upper alimentary canal are often a ccompanied by adenomas and adenocarcinomas of the lower intestine and bracken-grazing animals are also heavily immuno-suppressed, To elucida te the individual roles and the concerted action of the viral and chem ical factors involved in tumorigenesis and malignant conversion, we at tempted to reproduce experimentally the cancer syndrome observed in th e field. Florid persistent papillomatosis of the upper alimentary cana l was reproduced in animals infected with BPV-4 and immunosuppressed e ither by a diet of bracken or by treatment with azathioprine; cancer o f the upper alimentary tract or of the lower intestine developed only in animals infected with virus and fed on bracken fern. As in field ca ses, BPV-4 DNA was detected in papillomas but not in cancers. We concl ude that immunosuppression is necessary for persistence and spread of viral papillomas, that the fern mutagens are responsible for neoplasti c conversion of papilloma cells, and that continuous expression of vir al functions is not required for the maintenance of the malignant stat e.