All the strains of the Shope virus thus far tested which give rise to vigorous, progressively enlarging papillomas in domestic rabbits, function as carcinogenic agents by way of these growths. The more pathogenic the virus as evidenced by the brevity of its incubation period and the vigor of the papillomas produced, the sooner and oftener does cancer occur. The number of virus entities contained in the inoculum notably influences the outcome, cancer appearing most frequently in those confluent, papillomatous masses which have resulted from the greatest concentration of the virus material under test. The papillomas experimentally induced by the ordinary inoculation methods are essentially aggregates of proliferating cell families, each the outcome of some primary cell-virus association. Some of these associations are followed more frequently by cancer than others are in the same animal.
Cottontail rabbits, the natural hosts of the virus, are notably resistant to its sustained activity, as compared with domestic rabbits. Though often growing rapidly at first, the papillomas of cottontails soon become relatively inert in most cases, and they usually retrogress, and rarely undergo malignant change. In an instance here reported both a squamous cell carcinoma and a metastasizing sarcoma appeared at the base of some papillomas due to experimental inoculation, which had existed on the ears of a cottontail for nearly 2 years.
The meaning of the phenomena is discussed.