The Oncogenic Function of Mammalian Sarcoma Viruses

Abstract

The mammalian sarcoma viruses may serve as etiological factors in the development of naturally occurring tumors. Retroviruses capable of producing solid tumors in mammals have been isolated from naturally occurring neoplasms of mice, cats, and woolly monkey as well as from the solid tumors of mice and rats that developed in the course of in vivo passage of nontransforming C-type viruses. The significance of nontransforming C-type viruses in the generation of sarcoma viruses is stressed by the finding that replication-competent endogenous C-type viruses may be selected that at a high frequency participate in the generation of novel sarcoma viruses. The RNA genomes of mammalian viruses contain two distinct sets of nucleotide sequences. One component derives from a nontransforming replication-competent C-type virus, while the other set of sequences can be detected in the chromosomal DNA of the host of origin. The C-type viral genetic information of the mammalian transforming viruses is required for the proper replication of viral genomic RNA and may provide a promoter region for transcription. Sarcoma viruses and acute leukemia viruses of avian as well as mammalian origin are all recombinant viruses, whose genomes contain genetic information of a nontransforming C-type virus linked to sequences present in the chromosomal DNA of the host of origin. The generation of sarcoma viruses represents a special mode of disrupting controls exerted on cellular genetic information capable of acting as transforming genes. Altered expression of this cellular genetic information is also a key event in the cellular transformation induced by nonviral agents such as chemical carcinogens and physical agents.