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

• Published in: Radiation research 1991-05, Vol.126 (2), p.244-250
• Main Authors: Samid, Dvorit, Miller, Alexandra C., Rimoldi, Donata, Gafner, Jeffrey, Clark, Edward P.
• Format: Article
• Language: English
• Subjects: 3T3 cells; 560120 - Radiation Effects on Biochemicals, Cells, & Tissue Culture; ANIMAL CELLS; ANIMALS; Biological and medical sciences; Biological effects of radiation; BIOLOGICAL FUNCTIONS; CELL CYCLE; Cell growth; Cell lines; Cell Survival - radiation effects; Cell Transformation, Neoplastic - genetics; Dose-Response Relationship, Radiation; DOSE-RESPONSE RELATIONSHIPS; Fundamental and applied biological sciences. Psychology; GENE REGULATION; GENES; Genes, ras; Ionizing radiations; MAMMALS; MEMBRANE PROTEINS; MICE; NIH 3T3 cells; ONCOGENES; ORGANIC COMPOUNDS; PHENOTYPE; PROTEINS; Proto oncogenes; Radiation tolerance; Radiation Tolerance - genetics; RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT; RADIOSENSITIVITY; RNA; RODENTS; Somatic cells; Tissues, organs and organisms biophysics; Transformed cell line; VERTEBRATES
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3577825

The cellular Ha-ras oncogene, activated by missense mutations, has been implicated in intrinsic resistance to ionizing radiation. This study shows that the overexpression of the unmutated gene (proto-oncogene) may also be involved in how the cells respond to radiation. The experimental system consisted of mouse NIH 3T3-derived cell lines which carry multiple copies of a transcriptionally activated human c-Ha-ras proto-oncogene. Both tumorigenic (RS485) and revertant nontumorigenic subclones (PR4 and 4C3) which have high levels of ras expression exhibited a marked increase in radioresistance as measured by D0 compared to control NIH 3T3 cells. Other nontransformed cells with elevated levels of ras (phenotypically revertant line 4C8-A10) also had a significantly increased resistance to radiation, further indicating an association between ras and radioresistance. The increased radioresistance of the RS485 and phenotypic revertants could not be explained by a differential expression of the myc or metallothionein I genes or by variations in cell cycle. The correlation between increased ras proto-oncogene expression and radioresistance suggests that the ras encoded p21, a plasma membrane protein, may participate in the cellular responses to ionizing radiation.