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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.