Quantitative assessment of damage and radioprotection in primary human bronchial epithelial cells exposed to distinct ionizing radiation types

The effectiveness of radiotherapy for lung cancer is constrained by the inherent radiosensitivity of healthy lung tissue, presenting a significant clinical challenge. To improve our understanding of radiation exposure, there is a need for accurate representation of the native human lung response to radiation exposure as well as the effects of radioprotectant treatments. Here, we employed primary human bronchial epithelial cells in vitro to quantitatively assess damage and protection in response to ionizing radiation from two clinically relevant sources—gamma rays and X-rays—across doses ranging from 0 to 10 Gy. Subconfluent human bronchial epithelial cultures were exposed to 0–10 Gy of gamma radiation or X-rays, and cellular responses were assessed through morphological analysis, DNA damage quantification, and growth dynamics. Distinct biological effects were observed between radiation types, underscoring differences in damage profiles and cell sensitivity. We also investigated the protective effects of WR-1065, the active metabolite of Amifostine, as a model radioprotectant compound. Pre-treatment reduced radiation-induced injury, with differential efficacy depending on radiation type, reflecting the mechanisms of damage involved. Our findings demonstrate that primary human bronchial epithelial cells can report on radiation source-specific differences in cellular responses and radioprotectant efficacy. This system offers a physiologically-relevant and sensitive platform for evaluating the interplay of radiation exposure and radioprotectants with human airway cells in vitro .