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

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.