Increased radiation resistance in human osteosarcoma cells transformed by EJras oncogene

Alterations in ras oncogene expression have been associated with increased cellular resistance to ionizing radiation. As an extension of studies with murine cell models, we have now explored the radiation responses of human osteosarcoma cells (HOS) that differ in their EJras expression. Quantitative analysis revealed a tight correlation between the amounts of ras-encoded mRNA and protein p21 produced, and the degree of radioresistance. Inhibition of p21ras post- translational processing via inhibition of the mevalonate pathway with lovastatin, markedly decreased the cellular radiation resistance of these cells. The results indicate that elevation in the ras gene is necessary but not sufficient for maintenance of the radiation resistant phenotype; p21 must be membrane bound for these cells to maintain their increased radioresistance.