The Detectability and Survivability of Histone Modifications Induced by Low-Dose Ionizing Radiation
Kellogg, Benjamin Philip
The increasing likelihood of accidental or unplanned radiation exposure, where physicaldosimetry is unavailable, has increased the need for further identification of biological responsesspecific 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 histonesH3 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 sampleswere irradiated at doses of 5, 50, and 500 cGy using a dose-rate of .0607 Gy/min. All threeradiation sample groups were assayed using enzyme linked immunosorbent assay (ELISA)techniques to monitor the changes in post-translational modifications present in irradiatedsamples and non-irradiated, 0 cGy, control cells. Additionally, all three radiation sample groupswere measured at both 1 h and 24 h post-radiation to determine the survivability of histonemodifications after exposure. Each dose and time interval had three sample flasks containing10^7 cells for comparison against controls, this methodology increased the reliability of theresults. Irradiated samples were compared to controls to investigate any deviations in posttranslational modifications and then comparisons were made between time intervals to look formodification survivability between 1 h and 24 h. To establish a reliable biodosimeter, asubstantial 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 timeinterval when compared to controls. The H3ser10P modification at 500 cGy saw moderatedecreases 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 biomarkerfor low-dose exposure. These results suggest further study and larger sampling is necessarybefore a definitive conclusion can be made regarding the use of primary histone posttranslational modifications as a biomarker for low dose radiation damage.
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