Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: Ovarian cancer and space radiation
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Active - Currently funded and in progress
Procurement Mechanism(s):
Solicited
Aims:
Specific Aim 1: Utilize archived ovaries to compare ovarian tumor induction by irradiation with oxygen (16O), iron (56Fe), or g-rays and investigate the mouse strain dependence of ovarian tumor induction by 16O and 56Fe. Comparison of ovarian tumorigenesis in 3-month old C57BL/6J and B6C3F1 mice irradiated with 0.5 Gy 16O or 56Fe with 3-4 month old CB6F1 mice irradiated with 0.4, 0.8, 1.2, or 1.6 Gy g-rays, and concurrent controls, all euthanized 15-16 months after irradiation. We will conduct detailed histopathology of ovaries and molecular characterization of tumors using immunostaining for tumor markers. We will establish the relative biological effectiveness of charged 16O or 56Fe compared to g-radiation for ovarian tumorigenesis.

Specific Aim 2: Utilize archived ovaries harvested at various time points after irradiation
with low doses of 16O or 56Fe to examine the persistence of ovarian oxidative lipid, protein,
and DNA damage, archived serum to measure a biomarker of ovarian reserve, and evaluate
these as potential early biomarkers of ovarian tumorigenesis.
Our published work [Mishra et
al. 2016, Mishra et al. 2017] demonstrates oxidative damage and dose-dependent apoptotic
depletion of ovarian follicles after exposure to 0, 0.05, 0.3, and 0.5 Gy 16O or 56Fe, with estimated
ED50 for follicle depletion at one week after irradiation of 0.046 and 0.27 Gy, respectively. Serum
luteinizing hormone (LH) and follicle stimulating hormone (FSH) were significantly elevated in
0.5 Gy-irradiated mice 8wk after irradiation, consistent with loss of negative feedback due to
follicle depletion, but serum LH and FSH are not optimal serum markers of ovarian reserve
because they vary with estrous cycle stage and are secreted episodically, and we did not perform
immunohistochemical analyses of ovaries at 8 wk after irradiation. We will examine oxidative
lipid, protein, and DNA damage by immunostaining as potential biomarkers of ovarian tumor risk
in archived ovaries from mice euthanized 8 wk after irradiation with 16O and 56Fe. We will measure
Anti-Müllerian Hormone (AMH), a serum marker of ovarian reserve that is used clinically, in
archived serum from mice euthanized 1 wk and 15 months after irradiation.
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Mappings
RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
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RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
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RiskRisk of Radiation Carcinogenesis
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RiskRisk of Spaceflight Induced Cardiovascular Disease
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