In vitro exposure of human lens epithelial cells to X-rays at varied dose-rates leads to protein-level changes relevant to cataractogenesis

Abstract

Background Accumulated body of evidence shows that ionizing radiation increases the risk of cataracts. The mechanisms are not clear and the International Commission on Radiological Protection indicates a need for research into understanding the process, particularly at low doses and low dose rates of exposure. Purpose This study was designed to examine protein-level modifications in a human lens epithelial (HLE) cell-line following radiation exposures. Materials and methods HLE cell-line was subjected to X-irradiation at varied doses (0-5 Gy) and dose-rates (1.62 cGy/min and 38.2 cGy/min). Cells were collected 20 h post-exposure, lysed and proteins were clarified following fractionation by a molecular weight cut-off filtration method. Fractionated cellular proteins were enzymatically digested and subjected to mass spectrometry analysis. Results Statistically significant radiation dose-related protein changes compared to the control group were identified. Heatmap and hierarchical clustering analysis showed dose-rate dependant responses. Pathway analysis mapped the proteins to biological functions of mitochondrial dysfunction, reactive oxygen species generation, cell death, cancer, organismal injury and amyloidosis. Conclusion Overall findings suggest that ionizing radiation exposure of HLE cells by mediating dose rate-dependant oxidative stress and cell death-related mechanisms, can be relevant to cataractogenesis.