Interaction between bovine papillomavirus type 4 and cocarcinogens in the production of malignant tumours

Bovine fetal palatine tissue infected with bovine papillomavirus type 4 (BPV-4) was implanted subcutaneously in athymic nude mice. The implants developed into cysts containing papillomas essentially the same as those in the natural host. In order to investigate the interaction of cocarcinogens with BPV-4 in cell transformation, the virus-infected implants were exposed in vivo to either the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) or the tumour initiator 7,12-dimethylbenz[a]anthracene (DMBA). Papillomas were detected in a greater number of infected implants in the presence of either TPA or DMBA than in the absence of either of these chemicals indicating interaction between the virus and these two agents. Moreover, malignantly transformed cells arose with high frequency from infected implants that had been exposed to either chemical. In the presence of chemical and absence of virus or vice versa no neoplastic changes were seen histologically, indicating that cooperation between virus and cocarcinogen is required for transformation.