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47
New Biological Frontiers Illuminated by Molecular Sensors and Actuators
Poster Abstracts
13-POS
Board 13
Radiation-Induced Micronucleus in a Multi-Scale Tissue Modeling Framework
Shaowen Hu
, Ianik Plante.
Wyle Science, Technology and Engineering, Houston, USA.
The surface of skin is lined with several thin layers of epithelial cells that are maintained
throughout life time by a small population of stem cells. Ionizing radiation exposures could
injure the underlying proliferative cells and induce genomic instability that is correlated with
cancer risk. In this work a multi-scale computational model for skin epidermal dynamics that
links phenomena occurring at the subcellular, cellular, and tissue levels of organization is applied
to simulate the experimental data of cytokinesis-block micronucleus (CBMN) assay in 2 types of
3D in vitro human epidermal tissues. This multi-scale model has been used to simulate the
population kinetics and proliferation indexes observed in irradiated swine epidermis, which
highlights the importance of considering proliferation kinetics as well as the spatial organization
of tissues when conducting investigations of radiation responses. At the subcellular level, several
recently published Wnt signaling controlled cell-cycle models are applied, allowing testing of
validity of some basic biological rules at the cellular and sub-cellular levels by qualitatively
comparing simulation results with published data. We will present results of simulation of skin
responses of CBMN to conventional photon techniques as well as highly charged and energetic
(HZE) particles used in new Hadron therapy. Combining with the radiation track structure
simulated with software RITRACK, this approach could illuminate the roles of various physical,
chemical, and biological interactions in determining the relative biological effects of the HZE
particles to induce genomic instability. This integrated model will provide a versatile platform to
investigate various radiation altered physical, chemical, and biological interactions in different
time and spatial scales, which could enhance our understanding of the pathophysiological effects
of ionizing radiation on the skin for patients undergoing radiotherapy.