Neuron irradiation of Caenorhabditis elegans by protons triggers base excision repair pathway with limited effect on behaviour

Abstract

Proton therapy is increasingly used, due to its favourable physical properties such as the Bragg peak, which enable precise dose deposition while minimizing exposure to surrounding healthy tissues. One of the main indications for proton therapy is head and neck tumours. In addition to their therapeutic relevance, protons are also a key component of space radiation spectrum, raising concerns about their biological impact on normal tissues, particularly the central nervous system. Despite this growing concern, the effects of proton irradiation on adult post-mitotic neurons in vivo remain poorly understood. In this context, we analysed the impact of proton central nervous system micro-irradiation using the MIRCOM microbeam, in young adults of Caenorhabditis elegans, with a focus on DNA damage and behaviour. Protons induce localized oxidative DNA damage, confirmed by an increase in 8-oxoG signals within both the nuclei and cytoplasm of irradiated neurons. The biological response remained strictly confined to the targeted area; no signal propagation or damage was observed in neighbouring non-irradiated tissues. Despite molecular changes, there was no observable impact on behaviours such as motor activity, foraging, habituation, or touch-avoidance. These results suggest that proton exposure in post-mitotic neurons induces complex oxidative DNA damage and activates specific BER pathways without compromising functional behaviour or triggering systemic bystander effects. These insights are important for refining clinical radiation protection and understanding risks in space exploration.