Activation of endogenous C-type retroviral genomes by internal alpha-irradiation of mice with224Radium

Abstract

Sensitive cocultivation techniques were applied to study the radiation-induced activation of endogenous retroviral genomes in different mouse strains by the alpha-emitting radionuclide 224Radium. Activated infectious C-type retroviruses were detected in spleen, bone marrow and bone tissues of C57BL/6-, BALB/c- and NMRI mice. The titres of high-dose-irradiated animals were higher than those found in low-dose-irradiated animals. Infectious retrovirus could be detected with a dose of 13.2 rad (maximum dose rate 0.9 rad/day) in the skeleton, and a dose of 4.2 rad (maximum dose rate 0.3 rad/day) in the spleen. The virus activation pattern was different in the three mouse strains. These data indicate that activation of endogenous retroviral genomes by alpha-irradiation shows a dose-effect relationship and a dependence on the genetic background of the mouse.

Osteosarcomagenic doses of radium (224Ra) and infectious endogenous retroviruses enhance proliferation and osteogenic differentiation of skeletal tissue differentiating in vitro

“…In the early latent period of radiation-induced osteosarcomagenesis endogenous retroviruses are activated and infectious retroviruses are frequently isolated [29,32]. The long latency period of these tumors, together with molecular evidence for amplification and enhanced expression of several proliferation-associated genes in the tumors [37,39,40], indicate that a-irradiation is not sufficient for tumor induction.…”

“…Schmidt Studies of 224Ra-induced osteosarcomogenesis in mice have shown a dosedependent activation of endogenous retroviruses and the expression of infectious virus particles in bone during the latency period [29,32]. From the induced tumors, both acutely transforming, oncogene-bearing (v-onc) sarcoma viruses [8,9] and replication-competent retroviruses have been isolated [29,32]. These retroviruses exert distinct effects on skeletal mouse cells in vivo and in vitro [7,15,30,32,33], suggesting their critical role in radiation osteosarcomagenesis.…”

Amplification of endogenous proviral MuLV sequences in radiationinduced osteosarcomas

“…bridized under stringent conditions with 32P-labelled probes. The observation that non-transforming ecotropic murine leu-The Probe specific for the ecotropic Provirus [a 400-bP s m dkemia viruses (MuLV) were activated in a dose-dependent S m d fragment, coordinates 6.6-7.0 kbP of (Chattopadmanner during the early latency period of radiation-induced hYaY et al 198O)l was kindly Provided bY Dr. u. RaPP, NCI, osteosarcomas (Schmidt et al, 1985) indicates a role of endog-Frederick, MD. enous proviruses in those tumors.…”