Skip to page content Mission Information

EXPERIMENT INFORMATION

Duke NSCOR: Lung Cancer Risk from HZE Ions (NNX11AC60G)
Principal Investigator
Research Area:
Radiation health
Species Studied
Scientific Name: Mus musculus Species: Mouse

Description
OBJECTIVES:
The goal of this study was to understand mechanisms of high charge and energy (HZE) ion-induced lung cancer. To accomplish this goal, the Duke NSCOR brought together experts in radiation biology, lung cancer development, lung injury and repair, radiation dosimetry, and education. They combined sophisticated mouse genetics, in vivo lineage tracing, ex vivo isolation of lung epithelial progenitor cells, and analyses of lung cancers induced by HZE nuclei to dissect mechanisms of HZE ion-induced lung cancer. Investigators integrated three separate projects to understand how the cell of origin influences lung cancer development after HZE ion exposure, identify mechanisms of cellular response to HZE ions in different progenitor populations in the lung, and define how and when the p53 tumor suppressor, which is the most commonly mutated gene in human lung cancer, regulates HZE ion-induced carcinogenesis in the lung. Investigators anticipate that their hypothesis-based research will ultimately lead to the development of better models for HZE ion carcinogenic risk assessment for individual astronauts and novel approaches to prevent HZE ion-induced lung cancer through biological countermeasures.

In addition to studying lung cancer development, the Duke NSCOR also studied lung progenitor cell injury and repair after exposure to either terrestrial or space radiation. Injury and inflammation of the lung are key components of many diseases in people including emphysema, asthma, and lung fibrosis. Furthermore, patients receiving radiotherapy for either primary lung cancer or other neoplasms of the thoracic region (e.g. breast cancer) undergo lung tissue remodeling and declining lung function that is directly related to the dose and location of radiation exposure. By exploring which lung cells are injured by space radiation and how these injured lung cells are repaired, investigators anticipate that this knowledge may also lead to a better understanding of how lung diseases besides cancer develop and strategies that may be employed to moderate the effects of radiotherapy on lung tissue remodeling. This information may ultimately be used to develop novel approaches for the prevention and treatment of these lung diseases, and the improvement of public health.

This study had the following specific aims:

  1. Study the role and timing of the tumor suppressor p53 in radiation-induced lung cancer using mice with an extra copy of p53.
  2. study the role and timing of the tumor suppressor p53 in radiation-induced lung cancer using mice with an extra copy of p53 and reversible knockdown of p53.
  3. Develop a model of radiation-induced small cell lung cancer.


++ -- View more

Publications
Farin AM, Manzo ND, Terry KL, Kirsch DG, and Stripp BR. Low-and high-LET radiation drives clonal expansion of lung progenitor cells in vivo. Radiation Research. 2015. January; 183(1):124-32. pubmed.gov

Lee CL, Castle KD, Moding EJ, Blum JM, Williams N, Luo L, Ma Y, Borst LB, Kim Y, and Kirsch DG. Acute DNA damage activates the tumour suppressor p53 to promote radiation-induced lymphoma. Nature Communications. 2015. September 24; 6:8477. pubmed.gov

Asselin-Labat ML, Rampersad R, Xu X, Ritchie ME, Michalski J, Huang L, and Onaitis MW. High-LET radiation increases tumor progression in a K-Ras-driven model of lung adenocarcinoma. Radiation Research. 2017. November; 188(5):562-70. [DOI]

Moding EJ, Min HD, Castle KD, Ali M, Woodlief L, Williams N, Ma Y, Kim Y, Lee CL, and Kirsch DG. An extra copy of p53 suppresses development of spontaneous Kras-driven but not radiation-induced cancer. JCI Insight. 2016. July 7;1(10). [DOI]

Keywords
Cancer
Linear energy transfer (LET)
Lung
Radiation dosage
Radiation effects
++ -- View more

Data Information
Data Availability
Archive is complete. Data sets are not publicly available but can be requested.
Data Sets+ Request data

Parameters
HZE radiation
Lung progenitor cells
Tumor suppressor p53

Mission/Study Information
Mission Launch/Start Date Landing/End Date Duration
Ground 05/01/2009 In Progress

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/

+ Click here for information of how this experiment is contributing to the HRP's path for risk reduction.

Additional Information
Managing NASA Center
Johnson Space Center (JSC)
Responsible NASA Representative
Johnson Space Center LSDA Office
Project Manager: Terry Hill
Institutional Support
National Aeronautics and Space Administration (NASA)
Proposal Date
01/01/2011
Proposal Source
2010 Space Radiation NSCOR/Virtual NSCOR NNJ10ZSA002N