Janice L. Huff

How Safe Is Safe Enough? Radiation Risk for a Human Mission to Mars

Astronauts on a mission to Mars would be exposed for up to 3 years to galactic cosmic rays (GCR) — made up of high-energy protons and high charge (Z) and energy (E) (HZE) nuclei. GCR exposure rate increases about three times as spacecraft venture out of Earth orbit into deep space where protection of the Earths magnetosphere and solid body are lost. NASAs radiation standard limits astronaut exposures to a 3% risk of exposure induced death (REID) at the upper 95% confidence interval (CI) of the risk estimate. Fatal cancer risk has been considered the dominant risk for GCR, however recent epidemiological analysis of radiation risks for circulatory diseases allow for predictions of REID for circulatory diseases to be included with cancer risk predictions for space missions. Using NASAs models of risks and uncertainties, we predicted that central estimates for radiation induced mortality and morbidity could exceed 5% and 10% with upper 95% CI near 10% and 20%, respectively for a Mars mission. Additional risks to the central nervous system (CNS) and qualitative differences in the biological effects of GCR compared to terrestrial radiation may significantly increase these estimates, and will require new knowledge to evaluate.

Dendro(C 60 )fullerene DF-1 provides radioprotection to radiosensitive mammalian cells

In this study, the ability of the C60 fullerene derivative DF-1 to protect radiosensitive cells from the effects of high doses of gamma irradiation was examined. Earlier reports of DF-1’s lack of toxicity in these cells were confirmed, and DF-1 was also observed to protect both human lymphocytes and rat intestinal crypt cells against radiation-induced cell death. We determined that DF-1 protected both cell types against radiation-induced DNA damage, as measured by inhibition of micronucleus formation. DF-1 also reduced the levels of reactive oxygen species in the crypt cells, a unique capability of fullerenes because of their enhanced reactivity toward electron-rich species. The ability of DF-1 to protect against the cytotoxic effects of radiation was comparable to that of amifostine, another ROS-scavenging radioprotector. Interestingly, localization of fluorescently labeled DF-1 in fibroblast was observed throughout the cell. Taken together, these results suggest that DF-1 provides powerful protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, and cell death.

Galactic cosmic ray simulation at the NASA Space Radiation Laboratory

Most accelerator-based space radiation experiments have been performed with single ion beams at fixed energies. However, the space radiation environment consists of a wide variety of ion species with a continuous range of energies. Due to recent developments in beam switching technology implemented at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), it is now possible to rapidly switch ion species and energies, allowing for the possibility to more realistically simulate the actual radiation environment found in space. The present paper discusses a variety of issues related to implementation of galactic cosmic ray (GCR) simulation at NSRL, especially for experiments in radiobiology. Advantages and disadvantages of different approaches to developing a GCR simulator are presented. In addition, issues common to both GCR simulation and single beam experiments are compared to issues unique to GCR simulation studies. A set of conclusions is presented as well as a discussion of the technical implementation of GCR simulation.

The analysis of the densely populated patterns of radiation-induced foci by a stochastic, Monte Carlo model of DNA double-strand breaks induction by heavy ions

Purpose: To resolve the difficulty in counting merged DNA damage foci in high-LET (linear energy transfer) ion-induced patterns. Materials and methods: The analysis of patterns of RIF (radiation-induced foci) produced by high-LET Fe and Ti ions were conducted by using a Monte Carlo model that combines the heavy ion track structure with characteristics of the human genome on the level of chromosomes. The foci patterns were also simulated in the maximum projection plane for flat nuclei. Results: The model predicts the spatial and genomic distributions of DNA DSB (double-strand breaks) in a cell nucleus for a particular dose of radiation. We used the model to do analyses for three irradiation scenarios: (i) The ions were oriented perpendicular to the flattened nuclei in a cell culture monolayer; (ii) the ions were parallel to that plane; and (iii) round nucleus. In the parallel scenario we found that the foci appeared to be merged due to their high density, while, in the perpendicular scenario, the foci appeared as one bright spot per hit. The statistics and spatial distribution of regions of densely arranged foci, termed DNA foci chains, were predicted numerically using this model. Another analysis was done to evaluate the number of ion hits per nucleus, which were visible from streaks of closely located foci. Conclusions: We showed that DSB clustering needs to be taken into account to determine the true DNA damage foci yield, which helps to determine the DSB yield. Using the model analysis, a researcher can refine the DSB yield per nucleus per particle. We showed that purely geometric artifacts, present in the experimental images, can be analytically resolved with the model, and that the quantisation of track hits and DSB yields can be provided to the experimentalists who use enumeration of radiation-induced foci in immunofluorescence experiment using proteins that detect DNA damage.

Effects of sex and gender on adaptation to space: Immune system

This review is focused on sex and gender effects on immunological alterations occurring during space flight. Sex differences in immune function and the outcome of inflammatory, infectious, and autoimmune diseases are well documented. The work of the Immunology Workgroup identified numerous reasons why there could be sex and/or gender differences observed during and after spaceflight, but thus far, there has been very little investigation in this area of research. In most cases, this is due to either a low total number of subjects or the minimal number of female flight crew members available for these studies. Thus, the availability of a sufficient number of female subjects to enable statistical analysis of the data has been a limiting factor. As the inclusion of female crew members has increased in the recent past, such studies should be possible in the future. It is very difficult to obtain immunologic and infectious data in small animals that can be usefully extrapolated to humans undergoing spaceflight. Thus, it is recommended by the Immunology Workgroup that a greater emphasis be placed on studying astronauts themselves, with a focus on long-term evaluations of specific, known infectious risks.

Ionizing radiation enhances esophageal epithelial cell migration and invasion through a paracrine mechanism involving stromal-derived hepatocyte growth factor.

Esophageal cancer is the sixth leading cause of cancer death worldwide and the seventh leading cause of cancer death in the U.S. male population. Ionizing radiation exposure is a risk factor for development of esophageal squamous cell carcinoma, a histological subtype of esophageal cancer that is highly aggressive and is associated with poor patient prognosis. This study investigated the effects of ionizing radiation on the microenvironment and intercellular communication as it relates to esophageal carcinogenesis. We demonstrate that normal esophageal epithelial cells exhibited increased migration and invasion when cultured in the presence of irradiated stromal fibroblasts or with conditioned medium derived from irradiated stromal fibroblasts. Cytokine antibody arrays and ELISAs were used to identify hepatocyte growth factor (HGF) as an abundant protein that is secreted by esophageal fibroblasts at twofold increased levels in culture medium after γ irradiation. Reverse transcription qPCR analysis confirmed an approximately 50% increase in mRNA levels for HGF at 1 h in irradiated fibroblasts compared to unirradiated controls. Recombinant HGF stimulated increased wound healing, migration and invasion of esophageal epithelial cells, while blocking antibodies against HGF significantly decreased migration and invasion of epithelial cells in coculture with irradiated fibroblasts. Since HGF is known to direct cell migration, invasion and metastasis in a variety of tissues, including the esophagus, its modulation by ionizing radiation may have important implications for nontargeted pathways that influence radiation carcinogenesis in the esophagus.

AT cells are not radiosensitive for simple chromosomal exchanges at low dose

Cells deficient in ATM (product of the gene that is mutated in ataxia telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen breakage syndrome) show increased yields of both simple and complex chromosomal aberrations after high doses (>0.5Gy) of ionizing radiation (X-rays or γ-rays), however less is known on how these cells respond at low dose. Previously we had shown that the increased chromosome aberrations in ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex exchanges. The linear dose-response term for simple exchanges was significantly higher in NBS cells compared to wild type cells, but not for AT cells. However, AT cells have a high background level of exchanges compared to wild type or NBS cells that confounds the understanding of low dose responses. To understand the sensitivity differences for high to low doses, chromosomal aberration analysis was first performed at low dose-rates (0.5Gy/d), and results provided further evidence for the lack of sensitivity for exchanges in AT cells below doses of 1Gy. Normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed increased numbers of exchanges at a dose of 1Gy and higher, but were similar to wild type cells at 0.5Gy or below. These results were confirmed using siRNA knockdown of ATM. The present study provides evidence that the increased radiation sensitivity of AT cells for chromosomal exchanges found at high dose does not occur at low dose.

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts

Understanding space radiation health effects is critical due to potential increased morbidity and mortality following spaceflight. We evaluated whether there is evidence for excess cardiovascular disease or cancer mortality in early NASA astronauts and if a correlation exists between space radiation exposure and mortality. Astronauts selected from 1959–1969 were included and followed until death or February 2017, with 39 of 73 individuals still alive at that time. Calculated standardized mortality rates for tested outcomes were significantly below U.S. white male population rates, including all-cardiovascular disease (n = 7, SMR = 33; 95% CI, 14–65) and all-cancer (n = 7, SMR = 43; 95% CI, 18–83), as anticipated in a healthy worker population. Space radiation doses for cohort members ranged from 0–78 mGy. No significant associations between space radiation dose and mortality were found using logistic regression with an internal reference group, adjusting for medical radiation. Statistical power of the logistic regression was <6%, remaining <12% even when expected risk level or observed deaths were assumed to be 10 times higher than currently reported. While no excess radiation-associated cardiovascular or cancer mortality risk was observed, findings must be tempered by the statistical limitations of this cohort; notwithstanding, this small unique cohort provides a foundation for assessment of astronaut health.