Production and Release of Virus-Like Particles by Cultures of Agent-Free Ascites Cells<xref ref-type="fn" rid="FN2">2</xref>

Abstract

Virus-like particles in milk and breast tissue of agent-bearing mice but not in animals free from the agent suggest a causal relationship between these particles and mammary tumor development. The validity of this relationship was tested by use of a culture of mammary gland ascites tumor freed from the mammary tumor agent, as demonstrated with bioassay, by passage in agent-free mice for many years. These cells, propagated intraperitoneally in infected and agent-free hosts and examined with the electron microscope, failed to produce type A or B particles. When propagated subcutaneously for periods up to 31 days, type A particles were found in the cells irrespective of whether the host possessed the agent. Production of virus-like particles by monolayer cultures of these cells, when brought in contact with milk preparations containing or devoid of mammary tumor agent, or with buffer alone, was compared with the ability of respective culture fluids to produce mammary tumors when injected into susceptible agent-free female mice. The presence or absence of A and/or B particles from these cultures could not be correlated with the tumor-producing potential of the material under test. Material injected for assay contained many B particles. If the B particles are the agent, then the number injected should have resulted in a positive bioassay. Failure to obtain a positive bioassay from the tissue culture fluids in contact with cells propagated in vitro that are producing these particles, morphologically indistinguishable from those developing in vivo, may indicate: 1) Their synthesis from components in the media ordinarily foreign to the host imparts sufficient antigenicity to the particles to render them incapable of initiating the oncogenic process, or 2) these particles are a cellular product proliferated as a result of infection by the mammary tumor agent.