Ultra-low background radiation inhibits head and neck tumor via ATM downregulation mediated mitochondrial dysfunction

Natural background radiation is a pervasive element affecting biological organisms. However, the consequences of its absence are not well comprehended. This study investigates the effects of ultra-low background radiation on head and neck tumor cells using the China Jinping Underground Laboratory (CJPL), which effectively shields cosmic rays. Our results demonstrate that ultra-low background radiation significantly suppresses tumor cell proliferation and migration. Moreover, mitochondrial dysfunction is characterized by reduced membrane potential, impaired oxidative phosphorylation, and increased oxidative stress. Through RNA sequencing, the ATM gene is identified as a pivotal regulator in this process. Furthermore, the downregulation of ATM under ultra-low background radiation results in decreased expression of PGC-1α, NRF-1, and TFAM, all of which are associated with mitochondrial function. In contrast, the overexpression of ATM or TFAM partially ameliorates the inhibition of tumor cell behavior and mitochondrial function induced by ultra-low background radiation. Collectively, these findings demonstrate that ultra-low background radiation inhibits tumor cell behavior through mitochondrial dysfunction mediated by ATM downregulation, providing valuable insights into the potential therapeutic applications and molecular targets of ultra-low background radiation.