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Development of a combined model of tissue kinetics and radiation response of human bronchiolar epithelium with single cell resolutionOstrovskaya, Natela Grigoryevna 30 October 2006 (has links)
Lack of accurate data for epidemiological studies of low dose radiation effects
necessitates development of dosimetric models allowing prediction of cancer risks for
different organs. The objective of this work is to develop a model of the radiation
response of human bronchiolar tissue with single cell resolution. The computer model
describes epithelial tissue as an ensemble of individual cells, with the geometry of a
human bronchiole and the properties of different cell types are taken into account. The
model simulates the tissue kinetics and radiation exposure in four dimensions: three
spatial dimensions and a temporal dimension.
The bronchiole is modeled as a regular hollow cylinder with the epithelial cells
of three different types (basal, secretory, and ciliated) lining its interior. For the purposes
of assessment of radiation damage to the cells only the nuclei of the cells have been
modeled. Subroutines describing cellular kinetics have been developed to simulate cell
turnover in a normal epithelial tissue. Monte Carlo subroutines have been developed to
simulate exposure to alpha particles; the GEANT4 toolkit has been used to simulate exposure to low LET radiation. Each hit cell is provided with a record of energy
deposition, and this record is passed to the progeny if the cell survives.
The model output provides data on the number of basal progenitor cells in
different phases of a cell life-cycle and secretory to ciliated cell ratio after several
generations of cell proliferation. The model calculates labeling and mitotic indices and
estimates the average cell turnover time for the bronchiolar tissue. Microdosimetric
calculations are performed for cells traversed by ionizing particles. The model will be
used to assess the accumulation of damage in cells due to protracted low level radiation
exposure. The model output may provide directions for the future experimental design.
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