Nitric Oxide Is Involved in Heavy Ion-Induced Non-Targeted Effects in Human Fibroblasts

Previously, we investigated the dose response for chromosomal aberration (CA) for exposures corresponding to less than one particle traversal per cell nucleus by high energy and charge (HZE) particles, and showed that the dose responses for simple exchanges for human fibroblast irradiated under confluent culture conditions were best fit by non-linear models motivated by a non-targeted effect (NTE). Our results suggested that the simple exchanges in normal human fibroblasts have an important NTE contribution at low particle fluence. Nitric oxide (NO) has been reported as a candidate for intercellular signaling for NTE in many studies. In order to estimate the contribution of NTE components in induced CA, we measured CA with and without an NO scavenger in normal skin fibroblasts cells after exposure to 600 MeV/u and 1 GeV/u 56Fe ions, less than one direct particle traversal per cell nucleus. Yields of CA were significantly lower in fibroblasts exposed to the NO scavenger compared to controls, suggesting involvement of NO in cell signaling for induction of CA. Media transferred from irradiated cells induced CA in non-irradiated cells, and this effect was abrogated with NO scavengers. Our results strongly support the importance of NTE contributions in the formation of CA at low-particle fluence in fibroblasts. View Full-Tex

Race and Ethnic Group Dependent Space Radiation Cancer Risk Predictions

Future space missions by national space agencies and private industry, including space tourism, will include a diverse makeup of crewmembers with extensive variability in age, sex, and race or ethnic groups. The relative risk (RR) model is used to transfer epidemiology data between populations to estimate radiation risks. In the RR model cancer risk is assumed to be proportional to background cancer rates and limited by other causes of death, which are dependent on genetic, environmental and dietary factors that are population dependent. Here we apply the NSCR-2020 model to make the first predictions of age dependent space radiation cancer risks for several U.S. populations, which includes Asian-Pacific Islanders (API), Black, Hispanic (white and black), and White (non-Hispanic) populations. Results suggest that male API and Hispanic populations have the overall lowest cancer risks, while White females have the highest risk. Blacks have similar total cancer rates than Whites, however their reduced life expectancy leads to modestly lower lifetime radiation risks compared to Whites. There are diverse tissue specific cancer risk ranking across sex and race, which include sex specific organ risks, female’s having larger lung, stomach, and urinary-bladder radiation risks, and male’s having larger colon and brain risks

The NASA Radiation Interuniversity Science and Engineering(RaISE) Project: A Model for Inter-collaboration and Distance Learning in Radiation Physics and Nuclear Engineering

This viewgraph document reviews the Radiation Interuniversity Science and Engineering (RaISE) Project, which is a project that has as its goals strengthening and furthering the curriculum in radiation sciences at two Historically Black Colleges and Universities (HBCU), Prairie View A&M University and Texas Southern University. Those were chosen in part because of the proximity to NASA Johnson Space Center, a lead center for the Space Radiation Health Program. The presentation reviews the courses that have been developed, both in-class, and on-line

Uncertainties in Estimates of the Risks of Late Effects from Space Radiation

The health risks faced by astronauts from space radiation include cancer, cataracts, hereditary effects, and non-cancer morbidity and mortality risks related to the diseases of the old age. Methods used to project risks in low-Earth orbit are of questionable merit for exploration missions because of the limited radiobiology data and knowledge of galactic cosmic ray (GCR) heavy ions, which causes estimates of the risk of late effects to be highly uncertain. Risk projections involve a product of many biological and physical factors, each of which has a differential range of uncertainty due to lack of data and knowledge. Within the linear-additivity model, we use Monte-Carlo sampling from subjective uncertainty distributions in each factor to obtain a Maximum Likelihood estimate of the overall uncertainty in risk projections. The resulting methodology is applied to several human space exploration mission scenarios including ISS, lunar station, deep space outpost, and Mar's missions of duration of 360, 660, and 1000 days. The major results are the quantification of the uncertainties in current risk estimates, the identification of factors that dominate risk projection uncertainties, and the development of a method to quantify candidate approaches to reduce uncertainties or mitigate risks. The large uncertainties in GCR risk projections lead to probability distributions of risk that mask any potential risk reduction using the "optimization" of shielding materials or configurations. In contrast, the design of shielding optimization approaches for solar particle events and trapped protons can be made at this time, and promising technologies can be shown to have merit using our approach. The methods used also make it possible to express risk management objectives in terms of quantitative objective's, i.e., the number of days in space without exceeding a given risk level within well defined confidence limits

MARIE Measurements and Model Predictions of Solar Modulation of Galactic Cosmic Rays at Mars

Recent data from the MARIE (Martian Radiation Environment Experiment) instrument on board the 2001 Mars Odyssey spacecraft currently in Mars orbit are presented. It is shown that the short-term modulations of galactic cosmic rays (GCR) are well described by correlating the so lar modulation parameter, , with Earth-based neutron monitor counts using a 85-day time lag and the NASA Models - HZETRN (High Z and Energy Transport) and QMSFRG (Quantum Multiple Scattering theory of nuclear Fragmentation). The dose rates observed by the MARIE instrument are within 10% of the model calculations

Computational Model Prediction and Biological Validation Using Simplified Mixed Field Exposures for the Development of a GCR Reference Field

The yield of chromosomal aberrations has been shown to increase in the lymphocytes of astronauts after long-duration missions of several months in space. Chromosome exchanges, especially translocations, are positively correlated with many cancers and are therefore a potential biomarker of cancer risk associated with radiation exposure. Although extensive studies have been carried out on the induction of chromosomal aberrations by low- and high-LET radiation in human lymphocytes, fibroblasts, and epithelial cells exposed in vitro, there is a lack of data on chromosome aberrations induced by low dose-rate chronic exposure and mixed field beams such as those expected in space. Chromosome aberration studies at NSRL will provide the biological validation needed to extend the computational models over a broader range of experimental conditions (more complicated mixed fields leading up to the galactic cosmic rays (GCR) simulator), helping to reduce uncertainties in radiation quality effects and dose-rate dependence in cancer risk models. These models can then be used to answer some of the open questions regarding requirements for a full GCR reference field, including particle type and number, energy, dose rate, and delivery order. In this study, we designed a simplified mixed field beam with a combination of proton, helium, oxygen, and iron ions with shielding or proton, helium, oxygen, and titanium without shielding. Human fibroblasts cells were irradiated with these mixed field beam as well as each single beam with acute and chronic dose rate, and chromosome aberrations (CA) were measured with 3-color fluorescent in situ hybridization (FISH) chromosome painting methods. Frequency and type of CA induced with acute dose rate and chronic dose rates with single and mixed field beam will be discussed. A computational chromosome and radiation-induced DNA damage model, BDSTRACKS (Biological Damage by Stochastic Tracks), was updated to simulate various types of CA induced by acute exposures of the mixed field beams used for the experiments. The chromosomes were simulated by a polymer random walk algorithm with restrictions to their respective domains in the nucleus [1]. The stochastic dose to the nucleus was calculated with the code RITRACKS [2]. Irradiation of a target volume by a mixed field of ions was implemented within RITRACKs, and the fields of ions can be delivered over specific periods of time, allowing the simulation of dose-rate effects. Similarly, particles of various types and energies extracted from a pre-calculated spectra of galactic cosmic rays (GCR) can be used in RITRACKS. The number and spatial location of DSBs (DNA double-strand breaks) were calculated in BDSTRACKS using the simulated chromosomes and local (voxel) dose. Assuming that DSBs led to chromosome breaks, and simulating the rejoining of damaged chromosomes occurring during repair, BDSTRACKS produces the yield of various types of chromosome aberrations as a function of time (only final yields are presented). A comparison between experimental and simulation results will be shown

Radiation Matters of the Heart: A Mini Review

Radiation Therapy (RT) has been critical in cancer treatment regimens to date. However, it has been shown that ionizing radiation is also associated with increased risk of damage to healthy tissues. At high radiation doses, varied effects including inactivation of cells in treated tissue and associated functional impairment are seen. These range from direct damage to the heart; particularly, diffuse fibrosis of the pericardium and myocardium, adhesion of the pericardium, injury to the blood vessels and stenosis. Cardiac damage is mostly a late responding end-point, occurring anywhere between 1 and 10 years after radiation procedures. Cardiovascular disease following radiotherapy was more common with radiation treatments used before the late 1980s. Modern RT regimens with more focused radiation beams, allow tumors to be targeted more precisely and shield the heart and other healthy tissues for minimizing the radiation damage to normal cells. In this review, we discuss radiation therapeutic doses used and post-radiation damage to the heart muscle from published studies. We also emphasize the need for early detection of cardiotoxicity and the need for more cardio-protection approaches where feasible

Isotopic Dependence of GCR Fluence behind Shielding

In this paper we consider the effects of the isotopic composition of the primary galactic cosmic rays (GCR), nuclear fragmentation cross-sections, and isotopic-grid on the solution to transport models used for shielding studies. Satellite measurements are used to describe the isotopic composition of the GCR. For the nuclear interaction data-base and transport solution, we use the quantum multiple-scattering theory of nuclear fragmentation (QMSFRG) and high-charge and energy (HZETRN) transport code, respectively. The QMSFRG model is shown to accurately describe existing fragmentation data including proper description of the odd-even effects as function of the iso-spin dependence on the projectile nucleus. The principle finding of this study is that large errors (+/-100%) will occur in the mass-fluence spectra when comparing transport models that use a complete isotopic-grid (approx.170 ions) to ones that use a reduced isotopic-grid, for example the 59 ion-grid used in the HZETRN code in the past, however less significant errors (<+/-20%) occur in the elemental-fluence spectra. Because a complete isotopic-grid is readily handled on small computer workstations and is needed for several applications studying GCR propagation and scattering, it is recommended that they be used for future GCR studies