Ras regulation of radioresistance in cell culture

Abstract

This chapter describes the Ras regulation of radioresistance in cell culture. Some tumor cells have intrinsic resistance to killing by ionizing radiation and this may limit the effectiveness of radiation in cancer treatment. As many as 20% of patients who present with localized disease fail because of uncontrolled disease at the primary site, without signs of disseminated disease. One factor known to increase tumor cell resistance to radiation is the presence of activated oncogenes. Transfection with ras oncogenes is shown to increase radioresistance in certain rodent and human cells, although increased radioresistance was not seen in all cell types after ras transfection. Ras proteins are processed in a series of reactions that result in farnesylation or geranylgeranylation by farnesyltransferase or geranylgeranyltransferase, respectively. This is essential for the attachment of Ras to the inner surface of the plasma membrane and for activity. There is now ample evidence that Ras mutations contribute to radiation resistance in human cell lines. Activating mutations of ras can be seen in 30% of all human tumors.