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

Abstract

Cartilage tissue from embryonic mice which undergoes osteogenic differentiation during in vitro cultivation was used to study the effect of osteosarcomagenic doses of alpha-irradiation and bone-tumor-inducing retroviruses on proliferation and phenotypic differentiation of skeletal cells in a defined tissue culture model. Irradiated mandibular condyles showed dose-dependent enhancement of cell proliferation at day 7 of the culture and increased osteogenic differentiation at day 14. Maximal effects were found with 7.4 Bq/ml of 224Ra-labeled medium. Doses of 740 and 7400 Bq/ml of 224Ra-labeled medium induced increasing cell death. Retrovirus infection enhanced osteogenic differentiation and extended the viability of irradiated cells. After transplantation none of the treated tissues developed tumors in syngeneic mice.

Osteosarcomagenesis: Modeling Cancer Initiation in the Mouse

“…No particular oncogene appeared to predominate [44]. So important were these oncogenes felt to be initially that a theory became prominent in the literature during the 1980s and 1990s that radiation-induced osteosarcomagenesis may have as much to do with unsilencing of oncogenes as it does with DNA and chromosomal damage [45, 46]. …”