Transfection of rat embryo cells with mutant p53 increases the intrinsic radiation resistance.
Dominant oncogenic sequences have been shown to modulate the intrinsic radiation sensitivity of cells of both human and murine tumor cell lines. Whether transfection with candidate tumor-suppressor genes can modulate intrinsic radiation sensitivity is unknown. The data presented here demonstrate that transfection of rat embryo cells with a mutant p53 allele can increase the intrinsic radiation resistance of cells in vitro. First, transfection with mutant p53 resulted in transformed cellular morphology. Second, the transfected clone and the corresponding pooled population of transfected clones were more resistant to ionizing radiation in vitro. Last, analyses of the parameters of cell kinetics suggested that the radiobiological effects were unlikely to be due to altered parameters of cell kinetics at the time of irradiation, suggesting that mutant p53 altered the intrinsic radiation resistance of transfected cells by a more direct mechanism. Further experimentation will be necessary to develop a mechanistic approach for the study of these alterations.
Pardo
F S
FS
Department of Radiation Oncology, MGH Cancer Center, Massachusetts General Hospital/Harvard Medical School, Boston 02114.
Su
M
M
Borek
C
C
Preffer
F
F
Dombkowski
D
D
Gerweck
L
L
Schmidt
E V
EV
D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology; D016158:Genes, p53 / Q000502:physiology*; D009154:Mutation; D011836:Radiation Tolerance; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection