Charged-Iron-Particles Found in Galactic Cosmic Rays are Potent Inducers of Epithelial Ovarian Tumors

Abstract

Astronauts traveling in deep space are exposed to high-charge and energy (HZE) particles from galactic cosmic rays. We have previously determined that irradiation of adult female mice with iron HZE particles induces DNA double-strand breaks, oxidative damage and apoptosis in ovarian follicles, causing premature ovarian failure. These effects occur at lower doses than with conventional photon irradiation. Ovarian failure with resultant loss of negative feedback and elevated levels of gonadotropin hormones is thought to play a role in the pathophysiology of ovarian cancer. Therefore, we hypothesized that charged-iron-particle irradiation induces ovarian tumorigenesis in mice. In this study, three-month-old female mice were exposed to 0 cGy (sham) or 50 cGy iron ions and aged to 18 months. The 50 cGy irradiated mice had increased weight gain with age and lack of estrous cycling, consistent with ovarian failure. A total of 47% and 7% of mice irradiated with 50 cGy had unilateral and bilateral ovarian tumors, respectively, whereas 14% of mice in the 0 cGy group had unilateral tumors. The tumors contained multiple tubular structures, which were lined with cells positive for the epithelial marker cytokeratin, and had few proliferating cells. In some tumors, packets of cells between the tubular structures were immunopositive for the granulosa cell marker FOXL2. Based on these findings, tumors were diagnosed as tubular adenomas or mixed tubular adenoma/granulosa cell tumors. In conclusion, charged-iron-particle-radiation induces ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts.

Extraterrestrial Gynecology: Could Spaceflight Increase the Risk of Developing Cancer in Female Astronauts? An Updated Review

“…The tumors were tubular adenomas or mixed tubular adenoma/granulosa cell tumors. Though conclusions are limited by the dose rate, this study demonstrated a that space radiation analog can induce ovarian tumors in mice, raising concerns about ovarian tumors as late sequelae of deep space travel in female astronauts [142].…”

Nanotechnology enabled radioprotectants to reduce space radiation‐induced reactive oxidative species

“…Further, the forms of secondary radiation, triggered by GCRs, still possess significant penetrative potential and can accumulate more efficiently in biological tissues, as compared to primary GCRs (Slaba et al, 2017). GCR secondary radiation particles include beta particles, alpha particles, gamma rays, x-rays, neutrons, protons, and other particles with greater charge and mass (Mishra et al, 2018).…”

“…In vivo studies on low‐energy radiation from GCR observed stimulation of ovarian tumor formation in rat models (Mishra et al, 2018). Additionally, GCRs high penetrative capabilities make it possible for them to compromise central nervous system (CNS) structures and function.…”

Understanding the Effects of Deep Space Radiation on Nervous System: The Role of Genetically Tractable Experimental Models

“…HZE nuclei may strongly contribute to the carcinogenic risk to which crew members are exposed. Indeed, even at relatively low energy, iron ions are shown to be potent inducers of ovarian tumors formation in rodents [18]. Due to their high penetration power, GCR can efficiently reach CNS cells and pose a major risk to CNS function.…”