Tumour induction in the rodent Mastomys natalensis by activation of endogenous papilloma virus genomes

Abstract

Specific DNA sequences from human papillomavirus have recently been detected in carcinomas from epidermodysplasia verruciformis patients^1,2, and in vulvar³ and cervical^4,5 carcinomas but the role of papilloma viruses in the aetiology of these tumours is unclear. Indeed, little is known about the mechanisms that convert benign papillomas into malignant tumours and it is not even possible to distinguish between inactive passengers and viruses involved in tumour induction. Here, we describe an animal system that permits an analysis of the interaction of papilloma virus genomes with carcinogenic agents at the molecular level. In our colony of Mastomys natalensis (a close relative of the rat family), we have found extrachromosomal papilloma virus genomes persisting in a variety of tissues such as skin, muscle, liver and colon. With the ageing of the animals, the average copy number of viral DNA in skin cells increases and virus-producing tumours begin to appear in Mastomys at about 1 year old. This process is drastically enhanced by chronic treatment with a tumour promoter and transcription of the viral genomes has been found to be correlated with tumour formation.