Increased Radiation Resistance in Transformed and Nontransformed Cells withElevated ras Proto-Oncogene Expression

摘要

Understanding the molecular mechanisms of intrinsic radioresistance isfundamental to the development of potent chemical radioprotectors and the design of more effective cancer radiotherapy protocols. Recent studies have demonstrated a correlation radioresistance of human tumors and the expression of specific oncogenes, namely, the ras and raf oncogenes. Using DNA mediated gene transfer techniques, it has been shown that the activated raf may contribute to radioresistance in skin fibroblasts from cancer-prone individuals and in tumors of the head and neck. Furthermore, transfected raf and genes of the ras family (Ha-, Ki-, or N-ras) that are activated by missense mutations all induced a radioresistant phenotype in recipient rodent cells. This was in contrast to activated myc, fes and abl oncogenes, which had no effect on the response to radiation. Research efforts extending these observations by antisense RNA is sufficient for restoring radiosensitivity in human squamous carcinoma cells. It appears, therefore, that specific oncogenes may play a role in intrinsic radioresistance.