The Detectability and Survivability of Histone Modifications Induced by Low-Dose Ionizing Radiation

Abstract

The increasing likelihood of accidental or unplanned radiation exposure, where physical

dosimetry is unavailable, has increased the need for further identification of biological responses

specific to ionizing radiation that can be measured at very low doses, ideally 10 cGy or below.

This thesis will explore the use of gamma radiation to induce changes on the primary histones

H3 and H4 in the form of the post-translational modifications such as acetylation, methylation,

and phosphorylation. Human osteosarcoma cells were utilized for this study, and three samples

were irradiated at doses of 5, 50, and 500 cGy using a dose-rate of .0607 Gy/min. All three

radiation sample groups were assayed using enzyme linked immunosorbent assay (ELISA)

techniques to monitor the changes in post-translational modifications present in irradiated

samples and non-irradiated, 0 cGy, control cells. Additionally, all three radiation sample groups

were measured at both 1 h and 24 h post-radiation to determine the survivability of histone

modifications after exposure. Each dose and time interval had three sample flasks containing

10^7 cells for comparison against controls, this methodology increased the reliability of the

results. Irradiated samples were compared to controls to investigate any deviations in post

translational modifications and then comparisons were made between time intervals to look for

modification survivability between 1 h and 24 h. To establish a reliable biodosimeter, a

substantial histone response would be necessary at further time periods post-irradiation.

While some of the histone modifications showed scattered difference compared to controls,

none of them demonstrated consistent results across all three samples for each dose and time

interval when compared to controls. The H3ser10P modification at 500 cGy saw moderate

decreases compared to controls following irradiation . While this warrants further verification,

the results were not reproduced at the lower doses and limits the use of H3ser10P as a biomarker

for low-dose exposure. These results suggest further study and larger sampling is necessary

before a definitive conclusion can be made regarding the use of primary histone post

translational modifications as a biomarker for low dose radiation damage.