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Title: A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

Abstract

Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

Authors:
Publication Date:
Research Org.:
Texas A&M University Department of Nuclear Engineering
Sponsoring Org.:
USDOE
OSTI Identifier:
860179
Report Number(s):
DOE/ID/14329
TRN: US0702238
DOE Contract Number:
FG07-02ID14329
Resource Type:
Technical Report
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 61 RADIATION PROTECTION AND DOSIMETRY; 62 RADIOLOGY AND NUCLEAR MEDICINE; ACUTE EXPOSURE; APOPTOSIS; AVAILABILITY; CELL NUCLEI; CHRONIC EXPOSURE; DOSE RATES; KINETICS; RADIATIONS; RADIOTHERAPY; SIMULATION

Citation Formats

John R. Ford. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation. United States: N. p., 2005. Web. doi:10.2172/860179.
John R. Ford. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation. United States. doi:10.2172/860179.
John R. Ford. Tue . "A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation". United States. doi:10.2172/860179. https://www.osti.gov/servlets/purl/860179.
@article{osti_860179,
title = {A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation},
author = {John R. Ford},
abstractNote = {Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.},
doi = {10.2172/860179},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Tue Nov 01 00:00:00 EST 2005},
month = {Tue Nov 01 00:00:00 EST 2005}
}

Technical Report:

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  • The overall goal is characterization of 3D tissue models that can be used for investigation of the mechanisms underlying radiation-induced bystander effect at low doses (20 cGy or less) of low LET ionizing radiation, using a unique focused soft X-ray microprobe that had been upgraded to provide a range of focused soft X-ray energies, some sufficient to penetrate 3D models (Ref DE-FG02-01ER63236). The proposed studies will include an examination of whether the passage of a single electron track can trigger bystander responses in the 3D tissue models and, if so, whether the response is altered by increased or decreased levelsmore » of oxidative stress. Our existing multi-photon/confocal in-depth microscopy techniques will be used to develop assays for damage induced within intact 3D tissue models. The working hypothesis is that organization of cells into tissues, particularly involving more than one cell type, alters expression of the radiation-induced bystander effect compared to that seen in isolated single cell types in monolayer.« less
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  • Recent evidence suggests that prolonged exposures of exercising men to 0.08 ppm ozone (O3) result in significant decrements in lung function, induction of respiratory symptoms, and increases in nonspecific airway reactivity. The purpose of the study was to confirm or refute these findings by exposing 38 healthy young men to 0.08 ppm (O3) for 6.6 h. During exposure, subjects performed exercise for a total of 5 h, which required a minute ventilation of 40 l/min. Significant (O3)-induced decrements were observed for forced vital capacity (FVC, -0.25 1), forced expiratory volume in 1 s (FEV(sub 1.0), -0.35 l), and mean expiratorymore » flow rate between 25% and 75% of FVC (FEF(sub 25-75), -0.57 l/s), and significant increases were observed in airway reactivity (35%), specific airway resistance (0.77 cm H2O/s), and respiratory symptoms. These results essentially confirm previous findings. A large range in individual responses was noted (e.g., percentage change in FEV(sub 1.0): 4% increase to 38% decrease). Responses also appeared to be nonlinear in time under these experimental conditions.« less
  • Acute lower respiratory disease was surveyed by questionnaire among parents of 10,000 children aged 1 to 12 years in two Southeastern communities representing intermediate and high exposures to particulates and low sulfur dioxide levels. Morbidity reporting patterns with respect to age, parental education, and history of asthma were similar for blacks and whites, but the frequency of pneumonia was significantly lower, and the frequencies of croup, bronchitis, and 'any lower respiratory disease' were significantly higher among whites in both communities. Significant increases of any lower respiratory diseases and hospitalization were found among children in the high exposure community. Asthma ratesmore » clustered in families, were higher in male children and female parents, and were comparable to other studies. Significant increases of lower respiratory disease were also found among asthmatic children in the high exposure community. Difference in parental recall, family size, or parental cigarette smoking were not likely explanations for the excess morbidity in the high exposure community. Therefore, these results associate excess acute lower respiratory disease in children with exposure to elevated particulate levels and low sulfur dioxide concentrations.« less