A Comparison of Cs-137 γ Rays and 320-kV X-Rays in a Mouse Bone Marrow Transplantation Model

Abstract

US homeland security concerns regarding the potential misuse of some radiation sources used in radiobiological research, for example, cesium-137 (137Cs), have resulted in recommendations by the National Research Council to conduct studies into replacing these sources with suitable X-ray instruments. The objective of this research is to compare the effectiveness of an X-RAD 320 irradiator (PXINC 2010) with a 137Cs irradiator (Gammacell-1000 Unit) using an established bone marrow chimeric model. Using measured radiation doses for each instrument, we characterized the dose–response relationships for bone marrow and splenocyte ablation, using a cytotoxicity-hazard model. Our results show that the X-RAD 320 photon energy spectrum was suitable for ablating bone marrow at the 3 exposure levels used, similar to that of 137Cs photons. However, the 320-kV X-rays were not as effective as the much higher energy γ rays at depleting mouse splenocytes. Furthermore, the 3 X-ray levels used were less effective than the higher energy γ rays in allowing the successful engraftment of donor bone marrow, potentially as a result of the incomplete depletion of the spleen cells. More defined studies are warranted for determining whether bone marrow transplantation in mice can be successfully achieved using 320-kV X-rays. A higher X-ray dose then used is likely needed for transplantation success.

Modeling Cell Survival Fraction and Other Dose-Response Relationships for Immunodeficient C.B-17 SCID Mice Exposed to 320-kV X Rays

“…Studies using small animal models of hematopoietic system cell survival after exposure to X rays or γ rays has been a practice for decades and are important for bone marrow transplantation, medical counter measures, and other study-protocol planning. 32 Previously we performed successful bone marrow transplantation in Cs-137 γ-ray, split-dose exposed (bilaterally) C.B-17 immunocompetent anesthetized mice 5 but not with now-considered “not comparable” effective doses (based on an updated RBE estimate) of 320-kV X rays from the same X-RAD 320 irradiator as used in our present studies. Based on careful consideration of the research data generated, we think the most likely reason for the lack of success for 320 kV X rays was due to the RBE estimate (RBE = 1.3) used in the study design being too large, leading to the absorbed doses used being too small.…”

“…In this case, the magnitude of the positive slope decreases with increasing dose, which is characteristic of a mixed cell population with hyper-radiosensitive, moderately radiosensitive, and radioresistant cells (as appears to be the case for both bone marrow and spleen of C.B-17 mice). 5 , 12 For a negative exponential survival curve, H ck (D) is a linear-no-threshold (LNT) function of the radiation absorbed dose and therefore has no curvature .…”

“…25 For combined exposures to different radiation types or for combining results for different radiation sources (e.g., 137 Cs gamma ray and 320-kV X rays), a more complicated form of the HF model can also be employed using RBE-weighted dose and dose rate. 5 , 25 Changing dose rates from internal radionuclides can also be addressed with the more complicated form. 25…”

“…For X-ray cytotoxicity in vivo, R ck (D) corresponds to the ablation function A(D), as used in Gott et al 5 for immunocompetent C.B-17 mice. For characterizing the average live cell counts C(D) in bone marrow (or spleen) per unit body weight 1 day after radiation exposure as a function of absorbed dose D, an additional parameter C 0 can be used to represent the average live cell count per unit body weight among un-irradiated control replicates.…”

Comparable human reconstitution following Cesium-137 versus X-ray irradiation preconditioning in immunodeficient NOG mice

“…Moreover, research using higher doses implies that this niche is comprised of a large number of hypersensitive, modestly radiosensitive and resistant cells [ 3 ]. In essence, a relative biological effect (RBE) of around or above 1 is assumed for X-ray vs Cs-137 but differs between organs and in general estimated from studies which cannot be directly translated to ours [ 3 , 4 , 10 ]. Depending upon the experimental question, achieving the same biological effect from X-ray or Cs-137 is not necessarily associated with a one-to-one dose substitution or a simple conversation factor such as the RBE.…”