Host-Gene Control of C-Type Tumor Virus-Expression and Tumorigenesis: Relevance of Studies in Inbred Mice to Cancer in Man and Other Species

Abstract

C-type RNA viruses are tumorigenic in mice and other species. They are widespread and transmitted in an intimate relationship with host-cell genetic material. Tumorigenesis is no doubt a complex biological phenomenon, and involves both genetic and environmental factors. Among the genetic factors, single-locus determination is probably exceptional; yet, a number of genes are known in inbred mice and other species, including man, that can exert a major influence. Clearly, studies with inbred mice apply outside the murine model and justify generalizations on the etiology of cancer. The types of cancer observed in man are similar to those of inbred strains of mice, and their stochastic and often familial occurrences suggest that genetic factors play important roles in both man and mouse. A number of heritable disorders predipsose to tumorigenesis. Investigations of the relationship between various polymorphic phenotypes and human tumors should be intensified. For instance, a study of high-risk human-tumor groups could aid considerably not only in the recognition of etiological agents but also of underlying host-gene controlled mechanisms. Indeed epidemiological studies have already led to the identification of mutant genes that influence the incidence of human cancer. Such studies may be guided by findings in inbred strains of mice. There is good evidence in inbred mice that mutations in host chromosomes determine whether or not genes coding for RNA oncogene viral “functions” become expressed as cancer. Although an etiological role of C-type RNA virus has not yet been demonstrated in human cancer, studies of the interaction of viral and host-cell genomes in mice and other species, and the visualization of C-type virus in human tumors have provided good reasons for suspecting the presence in man of oncogenic genes (oncogenes) homologous to those of the C-type viral genomes, which are well studied in mice, hamsters, cats, rats, and chickens.