Increased radiation resistance in transformed and nontransformed cells with elevated ras proto-oncogene expression.
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.
Samid
D
D
Pathology Department, Uniformed Services University of The Health Sciences, Bethesda, Maryland.
Miller
A C
AC
Rimoldi
D
D
Gafner
J
J
Clark
E P
EP
D000818:Animals; D002470:Cell Survival / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004307:Dose-Response Relationship, Radiation; D011905:Genes, ras; D051379:Mice; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D011836:Radiation Tolerance / Q000235:genetics*