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|Title:||Low Dose Effects of Gamma and Neutron Radiation on Peripheral Blood Lymphocytes|
|Department:||Radiation Sciences (Medical Physics/Radiation Biology)|
|Abstract:||This thesis examines the effects of radiation on human peripheral blood lymphocytes, with the goal of elucidating a biomarker of radiation quality. The issues studied were (1) the effect of thermal and fast neutron exposure on chromosome aberrations, and (2) the effect of thermal neutron and gamma radiation on apoptosis and necrosis induction. As a starting point, a literature review was performed to examine how neutron RBE values vary with neutron energy, reference radiation, anticoagulant status, irradiation container, and RBE calculation method. The dicentric chromosome assay (DCA) was utilized for the microscope-based analysis of chromosome aberrations, whereas imaging flow cytometry was used to examine cell death. Chromosome aberrations were induced following both low dose 252Cf and thermal neutron irradiations (doses ranged between 10 mGy – 108 mGy and 1.2 mGy – 13.4 mGy, respectively), with both radiations demonstrating a linear relationship between dose and aberration induction. The results produced were compared to a pre-existing 137Cs dose response curve and indicated a RBE of 20.1 ± 2.9 for chromosome damage by 252Cf fast neutron radiation, and 26.1 ± 7.0 following low-dose thermal neutron exposure. When damage is assessed in lymphocytes via the dicentric chromosome assay, these results indicate that 252Cf is approximately 20 times more damaging than 137Cs gamma radiation, and thermal neutron radiation is approximately 26 times more damaging than 137Cs gamma radiation. In contrast, a RBE value could not be assigned to either apoptotic or necrotic induction following thermal neutron radiation, as no cell death dose-response was observed at doses between 0.2 mGy and 18.9 mGy. However, 60Co gamma doses between 0.03 Gy and 2.5 Gy demonstrated a quadratic dose-dependent increase for both types of cell death. Neither the chromosome aberration study nor the cell death study yielded a biomarker of radiation quality. While non-Poisson chromosome aberration over-dispersion of radiation-induced DNA aberrations is normally the result of either high-LET radiation exposure or a partial body exposure, it was found that neither the 252Cf nor the thermal neutron exposures consistently induced over-dispersion. As such, over-dispersion should not be used to differentiate high-and low-LET radiation exposures in lymphocytes. Unfortunately, due to a late-breaking thermal neutron dose rate decrease, it was not possible to assess whether the percentage of apoptosis and/or necrosis could be used as a biomarker of radiation quality, as the very low doses of thermal neutron radiation failed to demonstrate a significant dose response. That said, the 60Co cell death experiments demonstrated a linear-quadratic dose response for both apoptosis and necrosis at doses up to 2.5 Gy. Additionally, these experiments established that donor variability had little effect on cell death induction. This work contributes to our understanding of the biological effects of neutron and gamma radiation, and suggests that both thermal and fast neutron radiations induce chromosome aberrations in a dose-dependent manner. In contrast, it was found that in surviving cells at 48 hours post-irradiation, apoptosis and necrosis induction are independent of thermal neutron dose, a phenomenon that deserves further investigation. Additionally, since the low-dose 252Cf and thermal neutron DCA data failed to indicate consistent over-disperson typically characteristic of high-LET exposures, the results suggest that following accidental low-dose gamma exposures, estimates of dose, made using the DCA method, could be unreliable if the subject has a history of occupational exposures to neutrons.|
|Appears in Collections:||Open Access Dissertations and Theses|
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