Award Date

8-1-2020

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Health Physics and Diagnostic Sciences

First Committee Member

Janice Pluth

Second Committee Member

Steen Madsen

Third Committee Member

Francis Cucinotta

Fourth Committee Member

Patricia Cruz

Number of Pages

138

Abstract

Radiation-induced esophageal cancer can be a deadly and unfortunate secondary outcome of radiotherapy or chronic occupational exposure to radiation. Although the esophagus is known to be a radiosensitive organ, it is under studied and further information regarding how dose and radiation quality impact its sensitivity may provide strategies to prevent esophageal cancer. The purpose of this thesis was to understand factors that play a role in the tissue’s radiosensitivity that may relate to its cancer risk. In this study, we used two esophageal 3D models, as well as both human and mouse cells, to define radiation quality and dose dependent changes. The study details radiation-quality and dose dependent changes in: tissue morphology, MAPK/SAPK phospho-protein expression, crosstalk between the TGFβ and ATM pathways, and DNA damage kinetics. The results are complex, but provide not only radiation quality and dose dependent differences, but also species and cell type specific differences in response to radiation. The latter are especially critical to note when extrapolating results using different model systems. In total, the results suggest that esophageal tissue is sensitive to high vs. low linear energy transfer (LET) radiation. In addition, radiation induced changes in phospho-expression may underlie the changes in tissue morphology and result from alterations in proliferation and/or differentiation. Lastly, although a definitive answer underlying the rationale for the greater sensitivity of the esophagus to radiation was not defined, these studies have provided relevant key findings to pursue in future studies that should help to resolve this question.

Keywords

Cancer; Esophageal tissue; Radiation

Disciplines

Medicine and Health Sciences

File Format

pdf

File Size

12800 KB

Degree Grantor

University of Nevada, Las Vegas

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

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