PREDICTION OF RADIATION EXPOSURE FROM GENETIC EXPRESSION AND TREATMENT OF RESULTING CANCERS

Author

Adam Vanasse, University of Rhode IslandFollow

Date of Award

2024

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Physics

Specialization

Biophysics

Department

Physics

First Advisor

Michael Antosh

Abstract

In the absence of a physical device to measure radiation exposure, the general population has little to no efficient way of precisely measuring dose received long after the initial exposure. Even after this exposure, ionizing radiation greatly increases the likelihood of developing cancers and other health problems. This research focuses on three main experiments related to both tracking radiation exposure and treating the cancers that may arise from it.

The first of these experiments is an analysis of human blood samples irradiated at two different nuclear research facilities looking into the development of a biological dosimetry method. Using RNA sequencing, we analyze the genetic expression across all human genes to see the effect that increasing doses of radiation has on both individual genes and overarching biological functions. From these results we see several biological functions that show significant over expression as we increase the total dose, and several individual genes that display a linear dose-response effect that could be potential useful in determining dose long after the initial exposure.

We also investigate here the use of copper-cysteamine nanoparticles as a method of radiation enhancement for treating cancers. Copper cysteamine nanoparticles show strong potential use for cancer treatment because they aid in the production of toxic singlet oxygen molecules when exposed to various wavelengths of light. We utilize a nude mouse model where mice were injected with cancer cells subcutaneously. Once tumors formed, mice were given copper cysteamine nanoparticles either directly injected into the tumor, or via intravenous injection by a tail vein followed by 5 Gray of x-ray radiation in a cabinet x ray system. The overall size of tumors in mice was lower for any treated with radiation, but overlap in error analysis among nanoparticle treatment groups showed no significant impact in size reduction from the use of copper cysteamine nanoparticles.

Finally, we further investigate the use of copper cysteamine nanoparticles using a spheroid model. Spheroids are three-dimensional cell growths that better mimic a tumor environment than traditional two-dimensional cell cultures. We investigate their use as a treatment model using two different sizes of nanoparticles with 2 Gray of x ray radiation, followed by using only the larger of the particles at varying masses, still using 2 Gray. The larger particle size performed slightly better than the smaller particle size at limiting the growth of the spheroids, and the higher mass of those larger particle results in smaller sizes than using less mass but is strangely similar in size to those with no particles.

Recommended Citation

Vanasse, Adam, "PREDICTION OF RADIATION EXPOSURE FROM GENETIC EXPRESSION AND TREATMENT OF RESULTING CANCERS" (2024). Open Access Dissertations. Paper 1658.
https://digitalcommons.uri.edu/oa_diss/1658