Of birds and mice and men: comments on the use of animal models and molecular hybridization in the search for human tumor viruses Academic Article uri icon

Overview

MeSH Major

  • Disease Models, Animal
  • Neoplasms
  • Neoplasms, Experimental
  • Retroviridae

abstract

  • Current efforts to identify putative human tumor viruses rely heavily upon analogues provided by model systems from other species. These analogues should extend beyond aspects of viral structure per se, i.e. they should facilitate not merely the identification of virus particles in neoplastic tissue but the implication ofnviral genes in cancer genesis. This statement by summarizing the results of recent molecular studies on 2 animal models, Rous sarcoma virus of chickens (RSV) and the mammary tumor virus of mice (MMTV). A discussion of these models will be based on 2 current, not necessarily competing paradigms. The first holds that viral cancerogenesis is accomplished by the introduction of new genetic information into the cell. This paradigm is illustrated and well substantiated by the present knowledge of RSV. The second paradigm, popularly known as the 'oncogene hypothesis' circumvents the need for viral infection prior to cancerogenesis. Instead, it postulates that genes homologous to those present in the genomes of laboratory strains of RNS tumor viruses reside in the chromosomes of all normal cells. Normally repressed, some of these genes are cancerogenic when activated. The presence of C type viral genes in normal cells is now established fact, but the cancerogenic potential of these genes remains generally in doubt. MMTV provides an example of a system wherein the genetic potential for both tumorigenesis per se and the spontaneous production of an oncogenic virus are intrinsic to the genome of the host animal, but where exogenous infection by the same virus can also induce both virus replication and tumorigenesis. Both paradigms subsume the now widely accepted view that RNA tumor virus genes are perpetuated in the host cell as a DNA 'provirus'. This provirus is synthesized by a viral enzyme, an RNA directed DNA polymerase, or 'reverse transcriptase', and then integrated by covalent bonds into the chromosomal DNA of the host. Thereafter, the viral genes become subject to the same forms of expression and regulation as other, 'cellular' genes in the chromosome. The authors' findings and suggestions are summarized as follows. Infection of either duck or mammalian cells with Rous sarcoma virus introduces a new set of genes into the chromosomal DNA of the host cell. This event is a prerequisite for both replication of the virus and neoplastic transformation of the cells. By contrast, virus induced mammary carcinoma in the mouse can be inherited disease without requirement for genetic information beyond that already present in the mouse genome. This communication illustrates certain molecular correlates of the preceding biologic observations, and comments on the use of these correlates in designing and executing the search for RNA tumor viruses of man.

publication date

  • December 1974

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 4371153

Additional Document Info

start page

  • suppl:1421

end page

  • 6

volume

  • 34

number

  • 4 sup