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

US homeland security concerns related to potential misuse of γ-ray-emitting radiation sources employed in radiobiological research (eg, shielded cesium-137 irradiators) led to recommendations by the National Research Council to conduct studies into possibly replacing γ-ray irradiators used in research involving small rodent and other models with X-ray instruments. A limiting factor is suitability of the X-ray photon energy spectra. The objective of our research was to demonstrate the suitability of the radiation energy spectrum of 320-kV X rays after filtration (HVL = 4 mm Cu) for in-vivo cytotoxicity studies in immunodeficient C.B-17 SCID mice. By using a previously-published Hazard Function (HF) model to characterize dose-response relationships for in vivo bone marrow and spleen cell survival fractions and also to characterize the acute lethality risk (hematopoietic syndrome mode) we demonstrate that the filtered 320-kV X-ray beam appears suitable for such studies. A key finding for C.B-17 SCID mice when compared to results previously obtained for immunocompetent C.B-17 mice is that the immunodeficient mice appear to be more radioresistant, implicating a possible role of the immune system capacity in radiosensitivity of mammals.

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

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.

Kinetics equation replacement function for a particular continuous intake scenario.

An important paper by Skrable et al. included a retention function for compartment contents during a continuous intake, including the same time variable in both the numerator and denominator of the replacement function. In fact, the time in the denominator should have been represented as a constant describing the ultimate period length for the continuous intake, whether greater than, less than, or equal to the time variable for the associated measurement.

Internal dosimetry: a review.

The field history and current status of internal dosimetry is reviewed in this article. Elements of the field that are reviewed include standards and models, derivation of dose coefficients and intake retention fractions, bioassay measurements, and intake and dose calculations. In addition, guidance is developed and provided as to the necessity of internal dosimetry for a particular facility or operation and methodology for implementing a program. A discussion of the purposes of internal dosimetry is included as well as recommendations for future development and direction.

Internal dosimetry--a review.

The field history and current status of internal dosimetry is reviewed in this article. Elements of the field that are reviewed include standards and models, derivation of dose coefficients and intake retention fractions, bioassay measurements, and intake and dose calculations. In addition, guidance is developed and provided as to the necessity of internal dosimetry for a particular facility or operation and methodology for implementing a program. A discussion of the purposes of internal dosimetry is included as well as recommendations for future development and direction.

Application of the ICRP clarification of the tritium metabolic model.

In 2001, the International Commission on Radiological Protection published a clarification to the model for tritium metabolism. This clarification described the use of the gastrointestinal tract model, respiratory tract model, and transfer compartment in calculations of tritium metabolism. This information was used to derive intake retention fractions for tritium and tritium compounds including tritiated water, organically bound tritium, and tritides. In addition, dose coefficients were derived for tritide compounds including general categories described by the ICRP and some specific compounds.

Intake retention fractions developed from models used in the determination of dose coefficients developed for ICRP publication 68--particulate inhalation.

ICRP Publication 68 presents dose coefficients developed using systems of new models for the respiratory tract and metabolism of certain elements. The utility of these dose coefficients and associated models is limited without a method for calculating intake from bioassay results using the same models as in that publication. The calculation of a radionuclide intake requires values of expected fractions of the intake in bioassay samples collected at specific times after intake. The general system of models has been solved using a commercial software package and a method for solution of systems of first-order linear differential equations that uses eigenvectors and eigenvalues derived from the system of equations. The result of this work is a series of tables of fractions of acute inhalation intakes for different bioassay methods, times, and compound classes for intakes for those elements listed in ICRP Publication 68. The values in these tables can be used for intake calculations, development of bioassay frequencies, and development of action levels.

Development of a routine 125I bioassay program for athyrotic individuals using a pseudo uptake retention function.

Individuals working in iodine production require bioassay to determine if intakes have occurred. This is both to determine dose received for regulatory purposes and to verify whether workplace controls limiting the spread of contamination are adequate. Thyroid monitoring is commonly used as a bioassay technique to detect isotopes of iodine. If an individual performing iodine processing does not have a thyroid gland, other means must be used to determine intake and infer dose. Data was obtained from a previously published thesis that attempted to verify a model for absorption and retention of iodine by athyrotic individuals. These data were reevaluated to determine a pseudo uptake retention function. This analysis does not attempt to identify a biokinetic model, only to describe excretion of iodine and calculate an intake. Once the pseudo uptake retention function was derived, it was combined with the standard respiratory and gastrointestinal tract models as an inhalation intake retention function. A periodic urine bioassay protocol has been designed using the intake retention function described above and a conservative dose coefficient derived using organ dose coefficients for reference man, excluding the thyroid, and the appropriate weighting factors.