Inverse dose-rate effect of ionising radiation on residual 53BP1 foci in the eye lens

Sci Rep. 2019 Jul 18;9(1):10418. doi: 10.1038/s41598-019-46893-3.

Abstract

The influence of dose rate on radiation cataractogenesis has yet to be extensively studied. One recent epidemiological investigation suggested that protracted radiation exposure increases radiation-induced cataract risk: cumulative doses of radiation mostly <100 mGy received by US radiologic technologists over 5 years were associated with an increased excess hazard ratio for cataract development. However, there are few mechanistic studies to support and explain such observations. Low-dose radiation-induced DNA damage in the epithelial cells of the eye lens (LECs) has been proposed as a possible contributor to cataract formation and thus visual impairment. Here, 53BP1 foci was used as a marker of DNA damage. Unexpectedly, the number of 53BP1 foci that persisted in the mouse lens samples after γ-radiation exposure increased with decreasing dose-rate at 4 and 24 h. The C57BL/6 mice were exposed to 0.5, 1 and 2 Gy ƴ-radiation at 0.063 and 0.3 Gy/min and also 0.5 Gy at 0.014 Gy/min. This contrasts the data we obtained for peripheral blood lymphocytes collected from the same animal groups, which showed the expected reduction of residual 53BP1 foci with reducing dose-rate. These findings highlight the likely importance of dose-rate in low-dose cataract formation and, furthermore, represent the first evidence that LECs process radiation damage differently to blood lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cataract / metabolism
  • DNA Damage / radiation effects
  • Dose-Response Relationship, Radiation
  • Epithelial Cells / metabolism
  • Epithelial Cells / radiation effects
  • Female
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / radiation effects*
  • Lymphocytes / metabolism
  • Lymphocytes / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Radiation Dosage
  • Radiation Exposure
  • Radiation Injuries / metabolism*
  • Radiation, Ionizing
  • Tumor Suppressor p53-Binding Protein 1 / metabolism*

Substances

  • Trp53bp1 protein, mouse
  • Tumor Suppressor p53-Binding Protein 1