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Molecular and Histopathological Changes in Mouse Intestinal Tissue After Proton Exposure

Whole body exposure to protons in mice causes significant apoptosis in the crypts of the small intestine. Increasing numbers of crypts contained more apoptotic lesions as the dose of exposure increased. 16 genes associated with apoptotic pathways were shown to have significantly altered expression as compared to control samples for at least one of the doses of proton exposure 1 gene, Trp53inp1, was significantly up-regulated across all three doses. Those animals exposed to 0.1 Gy of proton irradiation showed greater amounts of significant alterations in gene expression as compared to 1 Gy and 2 Gy exposures. The differences in gene expression changes of low and high dose proton irradiated mice may offer insight into the molecular mechanisms of the possible high sensitivity at low proton doses. RAIDD (CRADD) may be responsible for the hypersensitivity observed in the duodenum of mice exposed to low doses of protons. Caspase-1 may also play a role in the hypersensitivity seen following proton irradiation at a dose of 0.1 Gy. FOXO3A may be involved in the down-regulation of GILZ observed at high doses of proton exposure.

Purgason, Ashley↗

Observation of the Radiation Environment and Solar Energetic Particle Events in Mars Orbit in May 2018- June 2022

Epithermal Neutron Detector (FREND). Here we present results from measurements of the charged particle fluxes, dose rates and estimation of dose equivalent rates at ExoMars TGO Mars science orbit, provided by Liulin-MO from May 2018 to June 2022. The period of measurements covers the declining and minimum phases of the solar activity in 24th solar cycle and the rising phase of the 25th cycle. Compared are the radiation values of the galactic cosmic rays (GCR) obtained during the different phases of the solar activity. The highest values of the dose rate and flux from GCR are registered from March to August 2020. At the minimum of 24th and transition to 25th solar cycle the dose rate from GCR is 15.9 ± 1.6 µGy h−1, particle flux is 3.3 ± 0.17 cm−2 s−1, dose equivalent rate is 72.3 ± 14.4 µSv h−1. Since September 2020 the dose rate and flux of GCR decrease. Particular attention is drawn to the observation of the solar energetic particle (SEP) events in July, September and October 2021, February and March 2022 as well as their effects on the radiation environment on TGO during the corresponding periods. The SEP event during15–19 February 2022 is the most powerful event observed in our data. The SEP dose during this event is 13.8 ± 1.4 mGy (in Si), the SEP dose equivalent is 21.9 ± 4.4 mSv. SEP events recorded in Mars orbit are related to coronal mass ejections (CME) observed by SOHO and STEREO A coronagraphs. Compared are the time profiles of the count rates measured by Liulin-MO, the neutron detectors of FREND and neutron detectors of the High Energy Neutron Detector (HEND) aboard Mars Odyssey during 15–19 February 2022 event. The data obtained is important for the knowledge of the radiation environment around Mars, regarding future manned and robotic flights to the planet. The data for SEP events in Mars orbit during July 2021-March 2022 contribute to the details on the solar activity at a time when Mars is on the opposite side of the Sun from Earth.

Jordanka Semkova↗

A comparison of quality factors and weighting factors for characterizing astronaut radiation exposures

Radiation exposures are typically characterized by two quantities. The first is the absorbed dose, or the energy deposited per unit mass for specific types of radiation passing through specified materials. The same amount of energy deposited in material by two different types of radiation, however, can result in two different levels of risk. Because of this, for the purpose of radiation protection operations, absorbed dose is modified by a second factor intended to normalize the risk associated with a given exposure. We present here an inter-comparison of methods for this modification. First is the radiation quality factor (Q), as defined by ICRP publication 60. This quantity is related functionally to the unrestricted linear energy transfer (LET) of a given radiation, and is multiplied by the absorbed dose to derive the dose equivalent (H). The second method for modifying absorbed dose is the radiation weighting factor, also given in ICRP-60, or as modified in NCRP report 115. To implement the weighting factor, the absorbed dose resulting from incidence of a particular radiation is multiplied by a factor assigned to that type of radiation, giving the equivalent dose. We compare calculations done based on identical fields of radiation representative of that encountered by the MIR space station, applying each of these two methods. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

NASA Center JSC↗

Chromosomal instability induced by heavy ion irradiation

PURPOSE: To establish the dose-response relationship for the induction of chromosomal instability in GM10115 cells exposed to high-energy iron ions (1 GeV/nucleon, mean LET 146 keV/microm) and gold ions (11 GeV/nucleon, mean LET 1450 keV/microm). Past work has established that sparsely ionizing X-rays can induce a long-lived destabilization of chromosomes in a dose-dependent manner at an incidence of approximately 3% per gray. The present investigation assesses the capacity of High-Z and High-energy (HZE) particles to elicit this same endpoint. MATERIALS AND METHODS: Clonal populations derived from single progenitor cells surviving heavy-ion irradiation were analyzed cytogenetically to identify those clones showing a persistent destablization of chromosomes. RESULTS: Dose-response data, with a particular emphasis at low dose (< 1.0 Gy), indicate a frequency of approximately 4% per gray for the induction of chromosomal instability in clones derived from single progenitor cells surviving exposure to iron ions. The induction of chromosomal instability by gold ions was, however, less responsive to applied dose, as the observed incidence of this phenotype varied from 0 to 10% over 1-8 Gy. Both iron and gold ions gave dose-dependent increases in the yield of chromosomal aberrations (both chromosome- and chromatid-type) measured at the first mitosis following irradiation, as well as shoulderless survival curves having D0=0.87 and 1.1 Gy respectively. CONCLUSIONS: Based on the present dose-response data, the relative biological effectiveness of iron ions is 1.3 for the induction of chromosomal instability, and this indicates that heavy ions are only slightly more efficient than X-rays at eliciting this delayed phenotype.

Non-NASA Center↗

Biomarkers of exposure, sensitivity and disease

PURPOSE: This review is to evaluate the use of biomarkers as an indication of past exposure to radiation or other environmental insults, individual sensitivity and risk for the development of late occurring disease. OVERVIEW: Biomarkers can be subdivided depending on their applications. Markers of exposure and dose can be used to reconstruct and predict past accidental or occupational exposures when limited or no physical measurements were available. Markers of risk or susceptibility can help identify sensitivity individuals that are at increased risk for development of spontaneous disease and may help predict the increased risk in sensitive individuals associated with environmental or therapeutic radiation exposures. Markers of disease represent the initial cellular or molecular changes that occur during disease development. Each of these types of biomarkers serves a unique purpose. OUTLINE: This paper concentrates on biomarkers of dose and exposure and provides a brief review of biomarkers of sensitivity and disease. The review of biomarkers of dose and exposure will demonstrate the usefulness of biomarkers in evaluation of physical factors associated with radiation exposure, such as LET, doserate and dose distribution. It will also evaluate the use of biomarkers to establish relationships that exist between exposure parameters such as energy deposition, environmental concentration of radioactive materials, alpha traversals and dose. In addition, the importance of biological factors on the magnitude of the biomarker response will be reviewed. Some of the factors evaluated will be the influence of species, tissue, cell types and genetic background. The review will demonstrate that markers of sensitivity and disease often have little usefulness in dose-reconstruction and, by the same token, many markers of dose or exposure may not be applicable for prediction of sensitivity or risk.

Non-NASA Center↗

Skeletal response to corticosteroid deficiency and excess in growing male rats

The study was designed to investigate bone histomorphometric changes induced by corticosteroid deficiency and supplementation at different dose levels in the rat skeleton. Male rats were adrenalectomized (ADX) or sham-operated and divided into six groups. At 2 days after surgery, sham-operated control rats (CON + PLA) and one group of ADX rats (ADX + PLA) were implanted subcutaneously (s.c.) with placebo pellets. ADX rats in the remaining four groups (ADX + C25, ADX + C50, ADX + C100, and ADX + C300) were implanted sc with corticosterone pellets designed to release 25, 50, 100, or 300 mg of the hormone over a 60 day period. Each ADX rat was also implanted sc with an aldosterone pellet (2.5 mg) similarly designed to release its contents over the same time period. All rats were killed at 3 weeks after implantation of pellets. Terminal blood samples were collected for serum biochemistry and the proximal tibial metaphyses (PTM), tibial diaphyses, and first lumbar vertebrae (LV) were processed undecalcified for quantitative bone histomorphometry. A dose-dependent increase in serum corticosterone concentration was observed in ADX rats implanted with hormone pellets. In comparison to CON + PLA rats, ADX + PLA rats had lower cancellous bone volume associated with a stimulation in longitudinal bone growth, an increase in mineral apposition rate, and a trend for increased osteoclast and osteoblast surfaces in PTM. In contrast, cancellous bone of ADX + C25 rats was preserved at nearly the CON + PLA level. However, the higher doses of corticosterone increased cancellous bone mass, but decreased longitudinal bone growth and all indices of bone resorption and formation in a dose-dependent manner in PTM. Similar cancellous bone changes were observed in the LV of corticosterone-treated rats, with the exception of a lack of an hormonal effect on cancellous bone mass. In the tibial diaphysis, corticosterone inhibited periosteal bone formation in a dose-dependent manner, but did not affect cortical bone mass. The results indicate that corticosteroid deficiency induces cancellous osteopenia, whereas supplementation with a near physiologic dose of the hormone prevents this bone loss in ADX rats. Furthermore, corticosteroid excess inhibits bone growth and bone turnover in a dose-dependent manner, but does not induce cancellous osteopenia in growing male rats.

Non-NASA Center↗

Cumulative Noise Metric Design Considerations for the Nasa Quesst Community Test Campaign With the X-59 Aircraft

The National Aeronautics and Space Administration (NASA) plans to collect X-59 aircraft dose-response data to inform international regulators in their efforts to establish acceptable noise standards to replace the current ban on overland supersonic commercial flight. For this upcoming community test campaign, the sound level from a supersonic overflight of the X-59 constitutes a single-event dose, and an end-of-day survey after multiple flight events constitutes a cumulative response. This study considers how X-59 community tests could be designed to explore the relationship between multiple single events and cumulative annoyance response. Presently, a day-night level summation of single-event doses formulates the cumulative dose; however, a generalization method may improve the understanding of the linkage between multiple single events and cumulative response. This work utilizes an analysis method that employs a parameter to vary the cumulative dose metric such that it can represent the loudest single event, remain as the day-night level summation, or be more responsive to the number of events. The analysis is demonstrated on simulated dose-response datasets derived from previous NASA field studies and from expectations of X-59 community tests. Results demonstrate that certain dose designs are more efficient than others in determining the analysis parameter.

dose-response modeling↗

Cumulative Noise Metric Design Considerations for the NASA Quesst Community Test Campaign With the X-59 Aircraft

The National Aeronautics and Space Administration (NASA) plans to collect X-59 aircraft dose-response data to inform international regulators in their efforts to establish acceptable noise standards to replace the current ban on overland supersonic commercial flight. For this upcoming community test campaign, the sound level from a supersonic overflight of the X-59 constitutes a single-event dose, and an end-of-day survey after multiple flight events constitutes a cumulative response. This study considers how X-59 community tests could be designed to explore the relationship between multiple single events and cumulative annoyance response. Presently, a day-night level summation of single-event doses formulates the cumulative dose; however, a generalization method may improve the understanding of the linkage between multiple single events and cumulative response. This work utilizes an analysis method that employs a parameter to vary the cumulative dose metric such that it can represent the loudest single event, remain as the day-night level summation, or be more responsive to the number of events. The analysis is demonstrated on simulated dose-response datasets derived from previous NASA field studies and from expectations of X-59 community tests. Results demonstrate that certain dose designs are more efficient than others in determining the analysis parameter.

dose-response modeling↗

Summary and Annotated Bibliography of Measurement Error Corrections with Potential Application in Future Quesst Mission Community Noise Studies

This document is motivated by likely needs of the Quesst mission community response tests, which will culminate in data collection and estimation of dose-response regression relationships for consideration by domestic and international aviation regulators. Furthermore, basic research questions evaluating interactions between rates of community annoyance, dose levels, and indicators of the presence of rattle, vibration, and startle hinge on hypothesis testing in the context of regression models. For a variety of reasons, noise doses may be known only imprecisely and may not reflect the actual level experienced by responding subjects. These differences between true dose and estimated dose, be they systematic or random, constitute covariate measurement error. Available statistics literature speaks to the impacts of measurement error on regression models, both in terms of bias in estimated coefficients and predicted values, and in terms of the loss of statistical power for hypothesis testing. Given the particulars of a categorical annoyance response variable and a continuous noise dose predictor variable subject to measurement error during testing, the emphasis of this report is on findings and methods pertinent to generalized linear (and mixed) models likely to be employed during the Quesst mission community tests. We reach the following conclusions: 1. Of four reviewed methods, structural Bayesian measurement error models and simulation extrapolation (SIMEX) may be the most readily applicable to Quesst mission community noise study objectives. 2. If warranted, a linear measurement model can help model systematic sources of measurement error that the classical measurement error does not. 3. For its ready implementation and small additional input requirements, simulation extrapolation may be ideally suited for addressing secondary research questions involving interactions between annoyance, noise dose, and other factors through hypothesis testing. 4. For their flexibility and ability to propagate uncertainty, structural Bayesian hierarchical models have great appeal for mission purposes; some care may be needed in developing appropriate probability models describing actual noise exposure during testing. An annotated bibliography logs additional papers and resources that may be of value to analysts in other projects and disciplines.

Dose-Response Model↗

Low-energy electron effects on tensile modulus and infrared transmission properties of a polypyromellitimide film

Infrared (IR) spectroscopy and tensile modulus testing were used to evaluate the importance of experimental procedure on changes in properties of pyromellitic dianhydride-p,p prime-oxydianiline film exposed to electron radiation. The radiation exposures were accelerated, approximate equivalents to the total dose expected for a 30 year mission in geosynchronous Earth orbit. The change in the tensile modulus depends more on the dose rate and the time interval between exposure and testing than on total dose. The IR data vary with both total dose and dose rate. A threshold dose rate exists below which reversible radiation effects on the IR spectra occur. Above the threshold dose rate, irreversible effects occur with the appearance of a new band. Post-irradiation and in situ IR absorption bands are significantly different. It is suggested that the electron radiation induced metastable, excites molecular states.

Ferl, J. E.↗

Linear response theory for annealing of radiation damage in semiconductor devices

A theoretical study of the radiation/annealing response of MOS ICs is described. Although many experiments have been performed in this field, no comprehensive theory dealing with radiation/annealing response has been proposed. Many attempts have been made to apply linear response theory, but no theoretical foundation has been presented. The linear response theory outlined here is capable of describing a broad area of radiation/annealing response phenomena in MOS ICs, in particular, both simultaneous irradiation and annealing, as well as short- and long-term annealing, including the case when annealing is nearing completion. For the first time, a simple procedure is devised to determine the response function from experimental radiation/annealing data. In addition, this procedure enables us to study the effect of variable temperature and dose rate, effects which are of interest in spaceflight. In the past, the shift in threshold potential due to radiation/annealing has usually been assumed to depend on one variable: the time lapse between an impulse dose and the time of observation. While such a suggestion of uniformity in time is certainly true for a broad range of radiation annealing phenomena, it may not hold for some ranges of the variables of interest (temperature, dose rate, etc.). A response function is projected which is dependent on two variables: the time of observation and the time of the impulse dose. This dependence on two variables allows us to extend the theory to the treatment of a variable dose rate. Finally, the linear theory is generalized to the case in which the response is nonlinear with impulse dose, but is proportional to some impulse function of dose. A method to determine both the impulse and response functions is presented.

Litovchenko, Vitaly↗

Radiation exposure of LDEF: Initial results

Initial results from LDEF include radiation detector measurements from four experiments, P0006, P0004, M0004, and A0015. The detectors were located on both the leading and trailing edges of the orbiter and also on the Earthside end. This allowed the directional dependence of the incoming radiation to be measured. Total absorbed doses from thermoluminescent detectors (TLDs) verified the predicted spatial east-west dose ratio dependence of a factor approx. 2.5, due to trapped proton anisotropy in the South Atlantic Anomaly. On the trailing edge of the orbiter a range of doses from 6.64 to 2.91 Gy were measured under Al equivalent shielding of 0.42 to 1.11 g/sq cm. A second set of detectors near this location yielded doses of 6.48 to 2.66 Gy under Al equivalent shielding of 0.48 to 15.4 g/sq cm. On the leading edge, doses of 2.58 to 2.10 Gy were found under Al equivalent shielding of 1.37 to 2.90 g/sq cm. Initial charged particle LET (linear energy transfer) spectra, fluxes, doses and dose equivalents, for LET in H2O greater than or = 8 keV/micron, were measured with plastic nuclear track detectors (PNTDs) located in two experiments. Also preliminary data on low energy neutrons were obtained from detectors containing (6)LiF foils.

Benton, E. V.↗

Radiation exposure predictions for long-duration-stay Mars missions

In this study, the ionizing radiation environment is estimated, using the Mission Radiation Calculation (MIRACAL) program, for several long-duration-stay Mars missions proposed for early in the 21st century. Both long-fast and minimum energy transfer missions are evaluated, and their 30-day maximum, annual maximum, and total slab skin and blood-forming organ (BFO) doses are compared. When large flares were included while the astronauts were on the surface, the delivered dose did not significantly contribute to the total dose (less than 4 cSv BFO dose, or 8 percent of the guideline annual limit, for the most energetic event simulated) due to the substantial protection provided by the Martian atmosphere. However, dose delivered by large flares during transit is dependent on vehicle shielding and distance from the sun. All of the long-fast transfer missions studied had lower total and annual maximum doses than the corresponding minimum energy transfer missions (on average, 30 percent less for missions having no large flares and the shielding thicknesses evaluated in this study). For all the missions studied, having the astronauts spend one-third of their day during transit in a 10 g/sq cm storm shelter resulted in significantly lower total doses.

Striepe, Scott A.↗

Radiation exposure predictions for long-duration-stay Mars missions

In this study, the ionizing radiation environment is estimated, using the Mission Radiation Calculation (MIRACAL) program, for several long-duration-stay Mars missions proposed for early in the 21(sup st) century. Both minimum energy and fast transfer missions are evaluated and their 30-day maximum, annual maximum, and total slab skin and blood-forming organ (BFO) doses are compared. When large flares were included while the astronauts were on the surface, the delivered dose did not significantly contribute to the total dose (less than 4 cSv BFO dose, or 8 percent of the guideline annual limit, for the most energetic event simulated) due to the substantial protection provided by the Martian atmosphere. However, dose delivered by large flares during transit is dependent on vehicle shielding and distance from the Sun. All of the fast transfer missions studied had lower total and annual maximum doses than the corresponding minimum energy transfer missions (on average, 30% less for missions having no large flares and the shielding thicknesses evaluated in this study). For all the missions studied, having the astronauts spend one-third of their day during transit in a 10 g/sq cm storm shelter resulted in an approximate 10% reduction in the total mission dose.

TOTAL SLAB SKIN↗

Martian Radiation Environment Experiment (MARIE)

Space radiation presents a very serious hazard to crews of interplanetary human missions. The two sources of this radiation are the galactic cosmic rays (GCR) and solar energetic particle (SEP) events. The GCR provides a steady source of low dose rate radiation that is primarily responsible for stochastic effects, such as cancer, and can effect the response of the central nervous system. Nuclear interactions of these components with the Martian atmosphere produces substantial flux of neutrons with high Radio Biological Effectiveness. The uncertainty in the knowledge of many fragmentation cross sections and their energy dependence required by radiation transport codes, uncertainties in the ambient radiation environment, and knowledge of the Martian atmosphere, lead to large enough uncertainties in the knowledge of calculated radiation dose in both free space (cruise phase), in Martian orbit, and on Martian surface. Direct measurements of radiation levels, the relative contributions of protons, neutrons, and heavy ions, and Martian atmospheric characteristics is thus a prerequisite for any human mission. An integrated suite of two spectrometers to provide these data will be described. The Orbiter spectrometer will measure the energy spectrum of SEP events from 15 to 500 MeV/n, and when combined with data from other space based instruments, such as the Advanced Composition Explorer (ACE), would provide accurate GCR spectra also. The Lander spectrometer would measure the absorbed dose rate, dose equivalent dose rate, and the linear energy transfer (LET) spectra and is capable of separating the relative contribution of these quantities from protons, neutrons, and high Z particles. There are two separate flight instruments, one for the Orbiter and one for the Lander, based on a common design of the backplane, the central processing unit (CPU), power supply, and onboard data storage. The Orbiter instrument consists of an energetic particle spectrometer that can measure the elemental energy spectra of charged particles over energy range of 15-500 MeV/n. The spectrometer will be mounted on the science deck and has an angular acceptance of 50 degrees. As the spacecraft orbits Mars, the axis of this field of view sweeps a cone of directions on the sky. During each orbit, the angle between the axis of the spectrometer's field of view and the mean interplanetary field direction varies from 90 degrees to 180 degrees. The Lander instrument is designed: (1) to measure the accumulated absorbed dose and dose rate in tissue as a function of time, (2) to determine the radiation quality factor, (3) to determine the energy deposition spectrum from 0.1 keV/micron to 1500 keV/micron, and (4) to separate the contribution of protons, neutrons, and HZE particles to these quantities.

Badhwar, Gautam D.↗

Radiation Effects on DC-DC Converters

In this work, several DC-DC converters were designed and built. The converters are Buck Buck-Boost, Cuk, Flyback, and full-bridge zero-voltage switched. The total ionizing dose radiation and single event effects on the converters were investigated. The experimental results for the TID effects tests show that the voltages of the Buck Buck-Boost, Cuk, and Flyback converters increase as total dose increased when using power MOSFET IRF250 as a switching transistor. The change in output voltage with total dose is highest for the Buck converter and the lowest for Flyback converter. The trend of increase in output voltages with total dose in the present work agrees with those of the literature. The trends of the experimental results also agree with those obtained from PSPICE simulation. For the full-bridge zero-voltage switch converter, it was observed that the dc-dc converter with IRF250 power MOSFET did not show a significant change of output voltage with total dose. In addition, for the dc-dc converter with FSF254R4 radiation-hardened power MOSFET, the output voltage did not change significantly with total dose. The experimental results were confirmed by PSPICE simulation that showed that FB-ZVS converter with IRF250 power MOSFET's was not affected with the increase in total ionizing dose. Single Event Effects (SEE) radiation tests were performed on FB-ZVS converters. It was observed that the FB-ZVS converter with the IRF250 power MOSFET, when the device was irradiated with Krypton ion with ion-energy of 150 MeV and LET of 41.3 MeV-square cm/mg, the output voltage increased with the increase in fluence. However, for Krypton with ion-energy of 600 MeV and LET of 33.65 MeV-square cm/mg, and two out of four transistors of the converter were permanently damaged. The dc-dc converter with FSF254R4 radiation hardened power MOSFET's did not show significant change at the output voltage with fluence while being irradiated by Krypton with ion energy of 1.20 GeV and LET of 25.97 MeV-square cm/mg. This might be due to fact that the device is radiation hardened.

Zhang, De-Xin↗

Radiation Tests of the Extravehicular Mobility Unit Space Suit for the International Space Station Using Energetic Protons

Measurements using silicon detectors to characterize the radiation transmitted through the EMU space suit and a human phantom have been performed using 155 and 250 MeV proton beams at LLUMC. The beams simulate radiation encountered in space, where trapped protons having kinetic energies on the order of 100 MeV are copious. Protons with 100 MeV kinetic energy and above can penetrate many centimeters of water or other light materials, so that astronauts exposed to such energetic particles will receive doses to their internal organs. This dose can be enhanced or reduced by shielding - either from the space suit or the self-shielding of the body - but minimization of the risk depends on details of the incident particle flux (in particular the energy spectrum) and on the dose responses of the various critical organs. Data were taken to characterize the beams and to calibrate the detectors using the beam in a treatment room at LLUPTF, in preparation for an experiment with the same beams incident on detectors placed in a human phantom within the EMU suit. Nuclear interactions of high-energy protons in various materials produce a small flux of highly ionizing, low-energy secondary radiation. Secondaries are of interest for their biological effects, since they cause doses and especially dose-equivalents to increase relative to the values expected simply from ionization energy loss along the Bragg curve. Because many secondaries have very short ranges, they are best measured in passive track detectors such as CR-39. The silicon detector data presented here are intended to supplement the CR-39 data in regions where silicon has greater sensitivity, in particular the portion of the LET spectrum below 5 keV/micron. The results obtained in this study suggest that optimizing the radiation shielding properties of space suits is a formidable task. The naive assumption that adding mass can reduce risk is not supported by the data, which show that reducing the dose delivered at or near the skin by low-energy particles may increase the dose delivered by energetic particles to points deeper in the body.

Zeitlin, C.↗

Biodosimetry as a New Paradigm for Determination of Radiation Risks and Risk-Mitigation in Astronauts Exposed to Space Radiation

Predicting risk of cancer in astronauts exposed to space radiation is challenging partly because uncertainties of absorption of dose and the processing of dose-related damage at the cellular level degrade the confidence of predicting the expression of cancer. Cellular biodosimeters that simultaneously report: 1) the quantity of absorbed dose after exposure to ionizing radiation, 2) the quality of radiation delivering that dose, and 3) the macromolecular profiles related to malignant transformation in cells absorbing that dose would therefore be useful. An approach to such a multiparametric biodosimeter will be reported, This is the demonstration of two dose-responsive field-effects of enhanced protein-expression. In one case, expression of keratin 18 (K18) in cultures of human mammary epithelial cells (HMEC) irradiated with cesium-137 gamma-rays is enhanced following exposure of log phase cells to relatively low doses of 30 to 90 cGy. K18 has been reported by a marker for tumor staging and for apoptosis. In the second case, expression of connexin 43 (Cx43) is increased in irradiated stationary phase cultures of HMEC, indicating enhanced formation of gap junctions. Gap junctions have been reported to be involved in bystander effects following irradiation. It is a biodosimeter for assessing radiogenic damage. It is suggested further that such biomolecular dosimetry may introduce a new paradigm for assessing cancer risk and risk-mitigation in individuals, a requirement for managing radiation health in astronauts during extended missions in space. This new paradigm is built upon the statistical power provided by the use of functional genomics and proteomics represented in combined gene- and protein-expression assays.

Richmond, Robert↗