Task Comparative Analysis of Charged Particle-Induced Autosomal Mutations in Murine Tissues and Cells (Completed)
Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: Murine Tissue
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Solicited
Aims:
Mutations are required in the transition from normal cells to cancer cells. Solid cancers in people arise primarily in epithelial cells. This proposal addresses the carcinogenic risk of exposure to energetic protons, the most abundant ion in galactic cosmic radiation (GCR) and solar particle events. The toxic effects of these exposures will also be measured. The studies outlined quantify mutation induction at a model, autosomal genetic locus (Aprt) located on mouse chromosome 8. C57BL/6 x DBA2 F1 Aprt heterozygous mice or kidney epithelial cells from this mouse strain will be irradiated to determine dose responses for cell killing and Aprt mutation in kidney epithelial cells exposed in the mice, or in kidney epithelial cells irradiated in culture. This will allow assessment of the role of the tissue microenvironment on modulation of mutation risk and on persistence of radiation-induced mutants in the kidney. Molecular analysis will determine the mechanisms leading to proton-induced Aprt mutants in exposed kidneys or in kidney cells irradiated in culture. It is predicted that proton exposure will result in mutants that lose the Aprt gene and other genes that are located in nearby regions of mouse chromosome 8. Studies are proposed to test if protracted exposure lessens the frequency of proton-induced mutants while also lowering the risk of killing kidney epithelial cells. The toxic and mutagenic effects of sequential exposure to protons and iron ions will be assessed (with iron ions serving as a representative heavy ion in the GCR) to test whether the risks are additive. Results from these studies will help reduce uncertainties in estimating the risk of cancer for astronauts exposed to protons alone or in mixed radiation fields. They will also provide detailed knowledge of the types of mutations that are created by these exposures that can contribute to the development of cancer.
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RiskRisk of Acute (In-flight) and Late Central Nervous System Effects from Radiation Exposure
You are here!TaskComparative Analysis of Charged Particle-Induced Autosomal Mutations in Murine Tissues and Cells

RiskRisk of Cardiovascular Disease and Other Degenerative Tissue Effects From Radiation Exposure and Secondary Spaceflight Stressors
You are here!TaskComparative Analysis of Charged Particle-Induced Autosomal Mutations in Murine Tissues and Cells

RiskRisk of Radiation Carcinogenesis
You are here!TaskComparative Analysis of Charged Particle-Induced Autosomal Mutations in Murine Tissues and Cells