Task HZE Radiation Effects on Malignant Progression in Human Epithelial Cells (Completed)
Last Published:  11/23/20 11:55:12 AM (Central)
Short Title: HZE Malignant Progression
Responsible HRP Element: Space Radiation
Collaborating Org(s):
Funding Status: Completed - Task completed and produced a deliverable
Procurement Mechanism(s):
Solicited
Aims:
Little is known about the mechanisms that underlie the greater biological effectiveness of high LET irradiation to promote solid cancer in experimental models. Our experimental data and that of others suggest that radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to the interaction of energy and DNA, while altered phenotypes and multicellular interactions that may contribute to cancer remain poorly defined. As recently reviewed by Hanahan and Weinberg, the hallmarks of cancer occur within very specific microenvironments that promote malignancy (Hanahan and Weinberg, 2011).

We hypothesize that both genetic and phenotypic changes contribute to radiation carcinogenesis. Radiation effects on critical phenotypes, if well understood, provide attractive targets for biological countermeasures because they represent processes that develop after radiation exposure and, unlike mutations, are amenable to intervention. We propose to study three aspects of neoplasia: tissue stem cells, phenotype, and genomic instability as a function of HZE particle irradiation of non-malignant epithelial cells co-cultured with irradiated human fibroblasts and/or macrophages.

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