Investigating the Effects of Particle Radiation Exposure on Lung Carcinogenesis
| dc.contributor.committeeMember | Shay, Jerry W. | en |
| dc.contributor.committeeMember | Chen, Benjamin P. | en |
| dc.contributor.committeeMember | Aroumougame, Asaithamby | en |
| dc.contributor.committeeMember | Akbay, Esra A. | en |
| dc.creator | Luitel, Krishna | en |
| dc.creator.orcid | 0000-0002-1393-2179 | |
| dc.date.accessioned | 2019-06-03T20:36:23Z | |
| dc.date.available | 2019-06-03T20:36:23Z | |
| dc.date.created | 2019-05 | |
| dc.date.issued | 2019-04-16 | |
| dc.date.submitted | May 2019 | |
| dc.date.updated | 2019-06-03T20:36:24Z | |
| dc.description.abstract | Lung cancer accounts for more cancer-related deaths than any other cancer type among both men and women. The overall increase in radiation risk for human cancer types has been substantiated by the epidemiological data obtained from atomic bomb survivors and uranium mine workers. The lung has a large surface area which makes it a prominent target for radiation exposure making it susceptible to radiation-induced cancer. Recently particle radiation therapy such as the use of protons and carbon has increased in the treatment of cancer. The long-term biological effects of proton radiation remain less well characterized in terms of radiotherapy and well as for astronauts during deep space explorations. We compared the long-term side effects of proton radiation to equivalent doses of X-rays in the initiation and progression of premalignant lesions in a transgenic mouse lung cancer model (K-rasLA1). We show proton irradiation causes more complex DNA damage that is not completely repaired resulting in increased oxidative stress in the lungs both acutely and persistently. Proton irradiated mice had lower median survival and increased carcinoma incidence as compared to un-irradiated controls or X-ray exposed mice. Additionally, the space radiation environment consists of a wide variety of ion species with a various range of energies. To understand the effects of mixed ion beam radiation, we exposed K-rasLA-1 mice with three ion beams: Proton (H), Helium (He), and Silicon (Si) at a low dose rate of 0.5cGy/min. Using the three ion beams, we performed whole body irradiation in two different orders: 3B-1 (H-He-Si) and 3B-2 (Si-He-H) and used only H as a reference. We found that whole-body irradiation with 3B-1 increases the incidence of cancer initiation and systemic oxidative stress in mice 100 days post-irradiation compared to 3B-2 and H irradiation. Additionally, we saw an increase in adenomas with atypia and adenocarcinomas in 3B-1 irradiated mice but not in 3B-2 and H irradiated mice. We also found that a non-toxic anti-inflammatory, anti-oxidative radioprotector (CDDO-EA) reduced 3B-1 induced oxidative stress and cancer initiation almost back to baseline. Thus, exposure to 3B-1 elicits significant changes in lung cancer initiation that can be mitigated using CDDO-EA. | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.oclc | 1103324532 | |
| dc.identifier.uri | https://hdl.handle.net/2152.5/6625 | |
| dc.language.iso | en | en |
| dc.subject | Disease Models, Animal | en |
| dc.subject | Inflammation | en |
| dc.subject | Lung Neoplasms | en |
| dc.subject | Neoplasms, Radiation-Induced | en |
| dc.subject | Protons | en |
| dc.title | Investigating the Effects of Particle Radiation Exposure on Lung Carcinogenesis | en |
| dc.type | Thesis | en |
| dc.type.material | text | en |
| thesis.degree.department | Graduate School of Biomedical Sciences | en |
| thesis.degree.discipline | Cancer Biology | en |
| thesis.degree.grantor | UT Southwestern Medical Center | en |
| thesis.degree.level | Doctoral | en |
| thesis.degree.name | Doctor of Philosophy | en |