Asma Rizvi

Abstract

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation (57^Co) to total doses of either 0.01 or 0.05 gray (Gy) and were subsequently exposed to simulated SPE protons. The protons were delivered over 36h and the dose rate profile mimicked the September 1989 solar flare. Proton energies ranged from 25 to 215 MeV and were delivered in 10 MeV increments to a total dose of either 1.7 Gy or 2 Gy. Our results showed that LDR can significantly ameliorate at least some adverse effects of SPE. Expression of p38MAPK and NF-κB were significantly increased and JNK expression was decreased in the group which was first primed with 0.01 Gy LDR before exposure to simulated SPE at 1.7 Gy.

There was also an increased production of IL-2 and IL-4 and decreased TGFβ production in the combination group as compared to groups which were exposed only to SPE. Evaluation of the TCR signaling pathway revealed that after 21 days post-irradiation LDR exposure had normalized LCK protein expression to control level, an effect not seen at the 4 day time point.

When we looked at the overall effect of LDR gamma-rays and simulated SPE protons on the major immune function cells, we found that different LDR doses had different effects. Priming with 0.01 Gy LDR resulted in a temporary decrease in the number of cells at day 4 post-exposure in both body compartments (spleen and blood), but by day 21 the counts were back to normal level. On the other hand, 0.05 Gy LDR appeared to be harmful; the T-lymphocytes were still low in the combination group even after 21 days post-radiation.

LLU Discipline

Microbiology and Molecular Genetics

School

Graduate Studies

First Advisor

Daila S. Gridley

Second Advisor

Kimberly J. Payne

Third Advisor

Lora M. Green

Fourth Advisor

Michael J. Pecaut

Fifth Advisor

Thomas A. Linkhart

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2008

Date (Title Page)

6-2008

Language

English

Library of Congress/MESH Subject Headings

T-Lymphocytes -- immunology; Radiation Effects; Mice; Protons; Adaptation, Psychological; Cell Aging -- radiation effects; Signal Transduction; Solar activity -- Statistical methods

Type

Dissertation

Page Count

xvii: 132

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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