DNA Damage Baseline Predicts Resilience to Space Radiation and Radiotherapy

Deep space exploration will require real-time, minimally invasive monitoring of astronaut health to mitigate the potential health impairments caused by space radiation and microgravity. Genotoxic stress in humans can be monitored by quantifying the amount of DNA double-strand breaks (DSBs) in immune cells from a simple finger prick. In a cohort of 674 healthy donors, we show that the endogenous level of DSBs increases with age and with latent cytomegalovirus infection. To map the range of human responses to space radiation, we then study DSB induction and repair in immune cells from 319 healthy donors after the cells are exposed to galactic cosmic ray components and lymphocytes from 30 cancer patients after radiotherapy. Individuals with low baseline DSB have fewer clinical complications, enhanced DNA damage repair responses, and a functional dose-dependent cytokine response in healthy donor cells. This supports the use of DSB monitoring for health resilience in space. [Display omitted] •Baseline DNA damage in human immune cells correlates with age and latent infection•Low baseline DNA damage results in better clinical outcomes after radiotherapy•Low baseline DNA damage correlates with stronger DNA repair response to irradiation•Low baseline DNA damage correlates with higher inflammatory cytokine dose response Pariset et al. find that individuals with a lower baseline level of DNA damage are resilient to clinical complications after radiotherapy and present higher radiation-induced levels of DNA repair foci and inflammatory cytokines. These findings support the use of baseline DNA damage as a biomarker for radiation sensitivity.