ONCOGENIC BASIS OF RADIATION-RESISTANCE

Oncogenes play an important role in the regulation of cellular resistance to ionizing radiation. This chapter reviews some of that evidence and attempt to formulate the themes underlying the oncogenic basis of radiation resistance. Cellular radiation sensitivity is a complex function of diverse molecular, biochemical, genetic, or environmental factors. Ionizing radiation induces multiple cellular and biological effects either by direct interaction with DNA or through the formation of free radical species leading to DNA damage. These effects include cell cycle-specific growth arrest, the repair of DNA damage, radical-scavenging proteins, gene mutations, malignant transformation, and cell killing. Some of these genes (ras, raf, cot, mos, and myc) demonstrate a cooperative effect toward radiation resistance. The possibility of a selective interaction among these proteins analogous to that involved in signal transduction leads to cell growth and proliferation or differentiation. Perturbations in the cell cycle (G1 or G2 arrest) and cell cycle-related proteins appear to be important factors contributing to cell survival. An important aspect of the radiation survival response is its regulation at the level of the cell cycle. The modulation of radiation resistance, mitogenic signals, radiation response, and causes or effects of radiation-resistant phenotype are also discussed in the chapter. © 1993, Academic Press Inc.