Activation of non-expressed bovine papilloma virus genomes by tumour promoters

Abstract

Naturally occurring cancer seems to be a multiple-hit phenomenon resulting from the interaction of several factors. Numerous environmental carcinogens on one hand and the widespread tumour viruses on the other, are capable of either transforming cells in vitro or inducing tumours in vivo. A few years ago, based on epidemiological evidence, a possible interaction between bovine papilloma viruses and an environmental carcinogen in bracken fern was noted in conjunction with alimentary cancer in cattle¹. We report here that tumour-promoting agents which by themselves are unable to transform cells, are capable of inducing the transcription of bovine papilloma virus type 1 (BPV-1) in mouse embryo fibroblast (MEF) tissue cultures, where the viral genomes reside in a non-expressed episomal state after infection. In such cells, one brief treatment with the tumour promoter results in the transcription of the same viral mRNA species present in BPV-1-induced tumours and in BPV-1-transformed cells. Furthermore, viral DNA is replicated and the cells acquire the transformed phenotype. Once activated, these properties remain stable. This interaction between tumour promoters and latent inactive tumour virus genomes leads, in appropriate cell systems, to the activation of particular viral genes and to the transformed phenotype of the host cells.