Simulation of GCR-Induced Harderian Gland and Lung Tumorigenesis (NNJ16HP22I)
Scientific Name: Mus musculus Species: Mouse Strain: B6CF1/Anl
One of the primary concerns impeding future missions to Mars and deep space exploration is the increased risk of cancer. Estimating crewmembers’ risk due to space radiation is limited to comparing crew health data to existing human epidemiological data on radiation-induced cancer and scaling human cancer risk from x-ray and gamma ray exposures that would be experienced in the space environment. Scaling calculations often assume a linear dose-response since the shape of the dose-response at doses below 100 mSv is unknown; however, preliminary analyses using silicon and titanium ions suggest a non-linear structure in the low dose zone for both Harderian and lung tumorigenesis. The goal of this study is to reduce uncertainties in the estimation of particle radiation carcinogenesis from galactic cosmic radiations (GCRs). To accomplish this, the investigators will collect data on the dose-response curve for heavy ion radiation in the low LET range and evaluate molecular endpoints in the tumors in order to elucidate the underlying mechanisms of particle radiation-induced oncogenesis.
This study has the following specific aims:
1a) Investigate the effects of a single beam 350 MeV/u OXYGEN (LET~20 keV/µm) alone at estimated 10%, 20%, and 30% tumor prevalence levels.
1b) Investigate the effect of two-beam combinations of three different ions (Protons with LET of
~0.4 keV/µm, Silicon ions with LET of ~70 keV/µm and Iron ions with LET of ~190 keV/µm) delivered within ~1.5 min of each other on the development of HG and lung tumors 16 months post-irradiation.
2) Carry out corresponding multi-component experiments, with the same beam energies as in
Aim 1, with at least three dose groups in addition to the sham-treated controls.
3) In silico modeling of mixed-beam and other experiments on tumor incidence. Theoretical modeling in parallel with Aims 1 and 2 will continue. It will emphasize deciding whether or not HG excess tumor prevalence due to a mixed beam can be approximately predicted from data and modeling on each component 1-ion species separately.
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This study will use existing Harderian gland (HG) tumorigenesis data and generate new HG tumorigenesis data exposed to heavy ion beams. Female CB6F1 murine cohorts were irradiated at between 100-120 days old and harvested after 16 months. Mice will be divided among three treatment cohorts: (1) single dose oxygen ions, (2) two-beam combinations of protons, silicon ions and iron ions, and (3) exposure to a combined GCR simulation mixed beam. The single dose oxygen ion cohort will be further split into three doses (20, 40, and 80 cGy). Data collected include the prevalence of tumors in the HG and lung tissues.
In silico modeling of tumor incidence in irradiated mice will assess the predictive capabilities of the mixed beam data and each component 1-ion species separately. Modeling will include the estimation of 95% confidence intervals and emphasize Monte Carlo simulation methods.
This experiment is currently in progress. Results will be available at the conclusion of the study.
Human Research Program (HRP) Human Research Roadmap (HRR) Information
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
and performance, providing essential countermeasures and technologies for human space exploration.
Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
and behavioral health support. The HRP utilizes an Integrated Research Plan (IRP) to identify
the approach and research activities planned to address these risks, which are assigned to specific
Elements within the program. The Human Research Roadmap is the web-based tool for communicating the IRP content.
The Human Research Roadmap is located at: https://humanresearchroadmap.nasa.gov/
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for information of how this experiment is contributing to the HRP's path for risk reduction.
Managing NASA Center
Ames Research Center (ARC)
Responsible NASA Representative
Ames Research Center LSDA Level 3
Project Manager: Sylvain Costes
National Aeronautics and Space Administration (NASA)
2014-15 HERO NNJ14ZSA001N