Activation and biological properties of endogenous retroviruses in radiation osteosarcomagenesis

Abstract

The activation of endogenous retroviruses (MuLV) by internal irradiation and the presence of activated retroviruses in radiation-induced murine osteosarcomas as well as their biological properties in vivo and in vitro were studied. Ecotropic and xenotropic MuLV were expressed dependent on the radiation dose in spleen, bone marrow and bone tissues of C57B1/6 mice after 224Ra treatment. Radiation-induced osteosarcomas of BALB/c, C57B1/6 and C3H × 101/F1 mice harboured infectious ecotropic and/or xenotropic viruses whereas in osteosarcomas of NMRI mice predominantly virus protein could be detected. In about 50% of the radiation-induced osteosarcomas of BALB/c mice an amplification of ecotropic proviruses could be detected. This was not found in clonally grown cells from non-tumorous tissues. MuLV from radiation-induced osteosarcomas induced osteopetrosis, osteomas and lymphomas after infection of newborn NMRI mice. In differentiating bone tissue the viruses were found to infect predominantly osteoblast precursor cells suggesting that virus infection results in increased growth and metabolic activity of these cells, which may be a possible mechanism for their pathogenic action in bone tissues.