Impairment of IGF-1 Signaling and Antioxidant Response Are Associated with Radiation Sensitivity and Mortality

Int J Mol Sci. 2021 Jan 5;22(1):451. doi: 10.3390/ijms22010451.


Following exposure to high doses of ionizing radiation, diverse strains of vertebrate species will manifest varying levels of radiation sensitivity. To understand the inter-strain cellular and molecular mechanisms of radiation sensitivity, two mouse strains with varying radiosensitivity (C3H/HeN, and CD2F1), were exposed to total body irradiation (TBI). Since Insulin-like Growth Factor-1 (IGF-1) signaling pathway is associated with radiosensitivity, we investigated the link between systemic or tissue-specific IGF-1 signaling and radiosensitivity. Adult male C3H/HeN and CD2F1 mice were irradiated using gamma photons at Lethal Dose-70/30 (LD70/30), 7.8 and 9.35 Gy doses, respectively. Those mice that survived up to 30 days post-irradiation, were termed the survivors. Mice that were euthanized prior to 30 days post-irradiation due to deteriorated health were termed decedents. The analysis of non-irradiated and irradiated survivor and decedent mice showed that inter-strain radiosensitivity and post-irradiation survival outcomes are associated with activation status of tissue and systemic IGF-1 signaling, nuclear factor erythroid 2-related factor 2 (Nrf2) activation, and the gene expression profile of cardiac mitochondrial energy metabolism pathways. Our findings link radiosensitivity with dysregulation of IGF-1 signaling, and highlight the role of antioxidant gene response and mitochondrial function in radiation sensitivity.

Keywords: IGF-1; Nrf2; mitochondria; oxidative stress; radiation injury.

MeSH terms

  • Animals
  • Antioxidants / metabolism*
  • Dose-Response Relationship, Radiation
  • Gamma Rays
  • Gene Expression / physiology
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mitochondria / metabolism
  • NF-E2-Related Factor 2 / metabolism
  • Radiation Tolerance / physiology*
  • Radiation, Ionizing
  • Signal Transduction / physiology*
  • Whole-Body Irradiation / methods


  • Antioxidants
  • NF-E2-Related Factor 2
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I