Effect of the insulin-like growth factor I receptor on ionizing radiation-induced cell death in mouse embryo fibroblasts

Exp Cell Res. 1997 Aug 25;235(1):287-94. doi: 10.1006/excr.1997.3683.


We have investigated the effect of the insulin-like growth factor I receptor (IGF-IR) on ionizing radiation (IR)-induced cell death using the following two mouse embryo fibroblast cell lines: (i) R- cells with a null mutation of the IGF-IR gene, therefore expressing no endogenous IGF-IR; (ii) R+ cells derived from R- cells, a stable transfectant overexpressing the human IGF-IR. Numbers of R- cells began to detach from dishes and float into the medium about 48 h after 10 Gy of X-irradiation. Internucleosomal DNA fragmentation detected by agarose gel electrophoresis, which is characteristic of apoptosis, was observed in the floating R- cells, but not in the attached cells. Unexpectedly, morphological analysis of the floating cells 72 h after irradiation revealed that only about half of them showed apoptotic death and the rest showed a nonapoptotic, presumably necrotic, one. On the other hand, R+ cells retained more than 90% viability even 4 days after irradiation, and very few floating cells were observed. The G2 arrest was induced in both cell lines following irradiation and G2/M fractions similarly returned to normal levels by around 20 h after irradiation, indicating that the cell death which appeared thereafter in R- cells is mediated through mitosis. Significant induction of p53 following irradiation was not detected by Western blot analysis in either R- or R+ cells. Collectively, these results demonstrate that signal transduction pathways originating from the IGF-IR may be involved in preventing IR-induced apoptosis and necrosis without affecting cell cycle arrest or p53 pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Adhesion / radiation effects
  • Cell Death / physiology
  • Cell Death / radiation effects*
  • Cell Division / radiation effects
  • Cell Survival / radiation effects
  • DNA Fragmentation
  • Dose-Response Relationship, Radiation
  • Embryo, Mammalian
  • Fibroblasts / cytology
  • Fibroblasts / physiology
  • Fibroblasts / radiation effects
  • Humans
  • Mice
  • Receptor, IGF Type 1 / biosynthesis
  • Receptor, IGF Type 1 / physiology*
  • Recombinant Proteins / biosynthesis
  • Time Factors
  • Transfection
  • Tumor Suppressor Protein p53 / biosynthesis
  • X-Rays


  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • Receptor, IGF Type 1