Planarians Develop Radiotolerance to Recurrent Ionizing Radiation Exposure

Abstract

Exposure to ionizing radiation can induce DNA fragmentation, leading to double-strand breaks, the most toxic form of DNA damage. Some organisms have developed mechanisms to overcome the adverse effects of ionizing radiation by enhancing DNA protection and repair. However, the underlying mechanisms driving radiation resistance to maintain genomic integrity and function remain poorly understood. Here, we provide evidence for the development of radiotolerance in the flatworm planarian Schmidtea mediterranea. We implemented a strategy to select animals capable of overcoming repeated rounds of ionizing radiation exposure. We demonstrate that planarians initially exposed to higher amounts of sub-lethal radiation can adapt, gaining the ability to recover reproductive capabilities faster than animals initially exposed to lower amounts of sub-lethal radiation. Our findings show that DNA integrity is reestablished in about one week after five cycles of sub-lethal ionizing radiation exposure. Planarian stem cells, known as neoblasts, can repair repeated DNA double-strand breaks by activating Rad51-mediated homologous recombination. The expression of the neoblast marker smedpiwi-1 and the mitotic activity reach levels similar to unirradiated animals between two and three weeks post-radiation. We describe that planarians develop radiotolerance through recurrent ionizing radiation exposure over several years and survive without apparent functional or morphological defects for an undetermined time.