Multistep nature of X-ray-induced neoplastic transformation in mammalian cells: genetic alterations and instability.
X-ray-induced neoplastic transformation has been studied in Syrian hamster embryo cells. Unirradiated cells had a limited life span, whereas the irradiated cells escaped senescence, showed altered morphology, and acquired anchorage-independence and tumorigenicity in a stepwise manner during successive transfers after irradiation. Multiple genetic changes may be associated with the expression of various transformed phenotypes. In fact, sequential alterations of various chromosomes were required for the malignant progression of irradiated cells. Oncogene activation was examined by the NIH3T3 transfection assay, no detectable changes having been identified so far. The only difference in oncogene expression detected was the augmented expression of the c-myc gene which was observed consistently. These findings indicate the multistep nature of X-ray-induced neoplastic transformation. Although the molecular changes involved in these process are still to be elucidated, recent studies have indicated that the instability induced by irradiation inherited through the progeny of irradiated cells is associated with those changes. This genetic instability provides a new way with which to elucidate the multistep process of radiation oncogenesis. The predicted mechanism and future studies are discussed.
Suzuki
K
K
Laboratory of Radiation and Life Science, School of Pharmaceutical Sciences, Nagasaki University, Japan.
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000528:radiation effects*; D003043:Cocarcinogenesis; D006224:Cricetinae; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D015398:Signal Transduction