One strategy to avoid track interactions is to lower the dose rate. By spacing out the time over which ions pass through a cell, breaks forming early in the time frame have an opportunity to be repaired before other breaks forming spatially close enough to interact with them arrive on the scene. This produces a reduction in the frequency of chromosome exchanges. As the dose rate decreases further a point is reached where virtually all the exchanges result from single track action. At this “limiting low dose rate” no additional reduction in chromosome exchange frequency is possible by further reduction in the dose rate. These results will be directly scalable to the low doses and dose rates present in space. Specific aim 1 of our proposal will endeavor to determine the limiting low dose rate for protons at the energy stated in the NRA (NASA Research Announcement). This will be accomplished by irradiating cells with a series of doses at dose rates we estimate will be close to the limiting low dose rate and looking for chromosome exchanges. When additional reduction in doses rate fails to produce any further decrease in exchanges as a function of dose we will be at the limiting low dose rate.

The GCR simulator will be irradiating samples with a number of different ion beams in order to better simulate the nature of the mixed ion field found in space. The heavier ions in the GCR spectrum will behave differently from the lighter ions. The heavy ions produce more damage along their tracks--so much so that virtually all chromosome exchanges are formed via single track action. In this case we will need to determine the optimal time needed for repair to occur between irradiations with the subsequent ion beams to avoid track interaction. Specific aim 2 will address these concerns by varying the time between ion beams. Much like the dose rate experiments, as we extend the time between irradiations, the probability for track interaction should be reduced. Once we reach a level where no further chromosome exchange frequency reductions are observed, we will have reached the optimal point for irradiation delay. Sequence may also be important in that regard and additional experiment will search for the best sequence that minimizes track interaction.

One strategy to avoid track interactions is to lower the dose rate. By spacing out the time over which ions pass through a cell, breaks forming early in the time frame have an opportunity to be repaired before other breaks forming spatially close enough to interact with them arrive on the scene. This produces a reduction in the frequency of chromosome exchanges. As the dose rate decreases further a point is reached where virtually all the exchanges result from single track action. At this “limiting low dose rate” no additional reduction in chromosome exchange frequency is possible by further reduction in the dose rate. These results will be directly scalable to the low doses and dose rates present in space. Specific aim 1 of our proposal will endeavor to determine the limiting low dose rate for protons at the energy stated in the NRA (NASA Research Announcement). This will be accomplished by irradiating cells with a series of doses at dose rates we estimate will be close to the limiting low dose rate and looking for chromosome exchanges. When additional reduction in doses rate fails to produce any further decrease in exchanges as a function of dose we will be at the limiting low dose rate.

The GCR simulator will be irradiating samples with a number of different ion beams in order to better simulate the nature of the mixed ion field found in space. The heavier ions in the GCR spectrum will behave differently from the lighter ions. The heavy ions produce more damage along their tracks--so much so that virtually all chromosome exchanges are formed via single track action. In this case we will need to determine the optimal time needed for repair to occur between irradiations with the subsequent ion beams to avoid track interaction. Specific aim 2 will address these concerns by varying the time between ion beams. Much like the dose rate experiments, as we extend the time between irradiations, the probability for track interaction should be reduced. Once we reach a level where no further chromosome exchange frequency reductions are observed, we will have reached the optimal point for irradiation delay. Sequence may also be important in that regard and additional experiment will search for the best sequence that minimizes track interaction.

A key factor in nature and severity of the effects produced is the spacing of the ionizations along the path or track that the ion takes through a cell. This is dependent on the mass and charge (the number of positively charged protons making up the ion) of the particle as well as the speed at which the ion is traveling. This spacing we refer to as linear energy transfer (LET) or the amount of energy that is used to produce ionizations along a specific length of the ion’s track. Ionizations are spaced far apart with low LET radiation but become increasingly closer together as LET increases.

A key concern to NASA is how dangerous is radiation to space flight crews. Most of the epidemiological data we have is from low LET radiations such as the X-rays used for radiation therapy or from the exposures received by the survivors the atomic bomb attacks in 1945. High LET data is harder to come by and derives largely from experiments using cells or animal model systems. These experiments use ground-based particle accelerators to accelerate ions to energies found in space and simulate potential space radiation exposures. Nearly all of this data come from experiments using a single ion at a solitary energy. As mentioned above, the space radiation environment is far more complex with many ions traveling with large ranges of energies all of which could impact an astronaut’s health, particularly since the probability of a cell in an astronaut’s body being hit sequentially by a small number of different ion species over a Mars mission lasting 600 to 900 days is quite high. In order to provide more realistic simulations of the space radiation environment, NASA is developing the GCR Simulator which has the potential to irradiate samples with multiple ion species within the shortest period of time allowed by ion switching, in order to mimic the effects of coincident (simultaneous) exposure. For the GCR simulator to best duplicate the natural space radiation environment, it is important to optimize dose delivery in ways that allow the results to be directly scalable to the low doses and dose rates that are encountered in deep space.

It will be difficult to match the low doses and dose rates directly. From a practical sense higher doses will need to be used in order to obtain statistically meaningful results. Likewise, higher dose rates are also required as exposing samples over long periods of time is just not feasible. Classically, the dose problem has been resolved by exposing samples to a series of higher doses then extrapolating the results back to the doses of interest. Similarly, it has long been known that as the dose rate declines the yield of biological endpoints is also diminished. This diminishment, however, only occurs to a point beyond which no additional decline in the dose response is detectable. The dose rate at which this point occurs has been termed the limiting low dose rate (LLDR). We plan to determine the LLDR for chromosome aberration induction by first measuring the dose response at high dose rate then using a mathematical model estimate the LLDR. The derived value for the LLDR will be tested in subsequent experiments. If we have achieved the LLDR the dose response will be strictly linear making extrapolations back to the conditions in the space radiation environment relatively straight forward. Future experiment will determine how best to fractionate the dose (deliver the dose in small increments with periods of time between each exposure) in a way that will achieve the same result as a continuous low dose rate exposure.

During the last year, travel restrictions implemented by the COVID-19 pandemic limited our ability to perform new experiments. We had planned to run low dose rate experiments to test the LLDR estimated from the results of last years high dose rate experiments. The original experiments scheduled for May 2020 had to be pushed back until November. Here we were able to complete experiments by shipping our cells to the NASA Space Radiation Laboratory (NSRL), have them irradiate them, then ship them back to us for processing and the generation of karyotypes where we could observe and tabulate the frequency of chromosome aberrations. While this experiment worked well, we were limited to only using fibroblasts (human skin cells). We would have liked to use lymphocytes as well (human white blood cells) but these would have required on site processing as they do not travel well. We were able to collect a large number of cells in mitosis (the phase of the cell cycle where we can see the chromosomes) and have begun working on producing the karyotypes for chromosomal analysis. This spring (2021) we plan to do additional experiments and hope to be able to travel again so we can get all the results we need from the lymphocytes.

One strategy to avoid track interactions is to lower the dose rate. By spacing out the time over which ions pass through a cell, breaks forming early in the time frame have an opportunity to be repaired before other breaks forming spatially close enough to interact with them arrive on the scene. This produces a reduction in the frequency of chromosome exchanges. As the dose rate decreases further a point is reached where virtually all the exchanges result from single track action. At this “limiting low dose rate” no additional reduction in chromosome exchange frequency is possible by further reduction in the dose rate. These results will be directly scalable to the low doses and dose rates present in space. Specific aim 1 of our proposal will endeavor to determine the limiting low dose rate for protons at the energy stated in the NRA (NASA Research Announcement). This will be accomplished by irradiating cells with a series of doses at dose rates we estimate will be close to the limiting low dose rate and looking for chromosome exchanges. When additional reduction in doses rate fails to produce any further decrease in exchanges as a function of dose we will be at the limiting low dose rate.

The GCR simulator will be irradiating samples with a number of different ion beams in order to better simulate the nature of the mixed ion field found in space. The heavier ions in the GCR spectrum will behave differently from the lighter ions. The heavy ions produce more damage along their tracks--so much so that virtually all chromosome exchanges are formed via single track action. In this case we will need to determine the optimal time needed for repair to occur between irradiations with the subsequent ion beams to avoid track interaction. Specific aim 2 will address these concerns by varying the time between ion beams. Much like the dose rate experiments, as we extend the time between irradiations, the probability for track interaction should be reduced. Once we reach a level where no further chromosome exchange frequency reductions are observed, we will have reached the optimal point for irradiation delay. Sequence may also be important in that regard and additional experiment will search for the best sequence that minimizes track interaction.

A key factor in nature and severity of the effects produced is the spacing of the ionizations along the path or track that the ion takes through a cell. This is dependent on the mass and charge (the number of positively charged protons making up the ion) of the particle as well as the speed at which the ion is traveling. This spacing we refer to as linear energy transfer (LET) or the amount of energy that is used to produce ionizations along a specific length of the ion’s track. Ionizations are spaced far apart with low LET radiation but become increasingly closer together as LET increases.

A key concern to NASA is how dangerous is radiation to space flight crews. Most of the epidemiological data we have is from low LET radiations such as the X-rays used for radiation therapy or from the exposures received by the survivors the atomic bomb attacks in 1945. High LET data is harder to come by and derives largely from experiments using cells or animal model systems. These experiments use ground-based particle accelerators to accelerate ions to energies found in space and simulate potential space radiation exposures. Nearly all of this data come from experiments using a single ion at a solitary energy. As mentioned above, the space radiation environment is far more complex with many ions traveling with large ranges of energies all of which could impact an astronaut’s health, particularly since the probability of a cell in an astronaut’s body being hit sequentially by a small number of different ion species over a Mars mission lasting 600 to 900 days is quite high. In order to provide more realistic simulations of the space radiation environment, NASA is developing the GCR Simulator which has the potential to irradiate samples with multiple ion species within the shortest period of time allowed by ion switching, in order to mimic the effects of coincident (simultaneous) exposure. For the GCR simulator to best duplicate the natural space radiation environment, it is important to optimize dose delivery in ways that allow the results to be directly scalable to the low doses and dose rates that are encountered in deep space.

It will be difficult to match the low doses and dose rates directly. From a practical sense higher doses will need to be used in order to obtain statistically meaningful results. Likewise, higher dose rates are also required as exposing samples over long periods of time is just not feasible. Classically, the dose problem has been resolved by exposing samples to a series of higher doses then extrapolating the results back to the doses of interest. Similarly, it has long been known that as the dose rate declines the yield of biological endpoints is also diminished. This diminishment, however, only occurs to a point beyond which no additional decline in the dose response is detectable. The dose rate at which this point occurs has been termed the limiting low dose rate (LLDR). We plan to determine the LLDR for chromosome aberration induction by first measuring the dose response at high dose rate then using a mathematical model estimate the LLDR. The derived value for the LLDR will be tested in subsequent experiments. If we have achieved the LLDR the dose response will be strictly linear making extrapolations back to the conditions in the space radiation environment relatively straightforward. Future experiment will determine how best to fractionate the dose (deliver the dose in small increments with periods of time between each exposure) in a way that will achieve the same result as a continuous low dose rate exposure.

During the last year we were able conduct our high dose rate experiments which we will use to estimate the LLDR through use of the G-function. We irradiated both human lymphocytes (white blood cells) and fibroblasts (skin cells) with 1 GeV protons or 250 MeV/n Helium ions. We collected mitotic cells (cells undergoing mitosis when the chromosomes are visible) from these populations and analyzed them for the presence of chromosome aberrations. These were tabulated and dose responses were constructed. We then applied a mathematical model to these results and came up with estimates for the LLDR. Based on our model, we estimate the LLDR for protons will be about 0.01 cGy/min. As this rate is likely to be too low to deliver experimentally, we will be using a rate of 0.1 cGy/min for tests scheduled for May of 2020. Analysis of the Helium ion results is on-going, and we hope to have these completed soon.

One strategy to avoid track interactions is to lower the dose rate. By spacing out the time over which ions pass through a cell, breaks forming early in the time frame have an opportunity to be repaired before other breaks forming spatially close enough to interact with them arrive on the scene. This produces a reduction in the frequency of chromosome exchanges. As the dose rate decreases further a point is reached where virtually all the exchanges result from single track action. At this “limiting low dose rate” no additional reduction in chromosome exchange frequency is possible by further reduction in the dose rate. These results will be directly scalable to the low doses and dose rates present in space. Specific aim 1 of our proposal will endeavor to determine the limiting low dose rate for protons at the energy stated in the NRA (NASA Research Announcement). This will be accomplished by irradiating cells with a series of doses at dose rates we estimate will be close to the limiting low dose rate and looking for chromosome exchanges. When additional reduction in doses rate fails to produce any further decrease in exchanges as a function of dose we will be at the limiting low dose rate.

The GCR simulator will be irradiating samples with a number of different ion beams in order to better simulate the nature of the mixed ion field found in space. The heavier ions in the GCR spectrum will behave differently from the lighter ions. The heavy ions produce more damage along their tracks--so much so that virtually all chromosome exchanges are formed via single track action. In this case we will need to determine the optimal time needed for repair to occur between irradiations with the subsequent ion beams to avoid track interaction. Specific aim 2 will address these concerns by varying the time between ion beams. Much like the dose rate experiments, as we extend the time between irradiations, the probability for track interaction should be reduced. Once we reach a level where no further chromosome exchange frequency reductions are observed, we will have reached the optimal point for irradiation delay. Sequence may also be important in that regard and additional experiment will search for the best sequence that minimizes track interaction.

A key factor in nature and severity of the effects produced is the spacing of the ionizations along the path or track that the ion takes through a cell. This is dependent on the mass and charge (the number of positively charged protons making up the ion) of the particle as well as the speed at which the ion is traveling. This spacing we refer to as linear energy transfer (LET) or the amount of energy that is used to produce ionizations along a specific length of the ion’s track. Ionizations are spaced far apart with low LET radiation but become increasingly closer together as LET increases.

A key concern to NASA is how dangerous is radiation to space flight crews. Most of the epidemiological data we have is from low LET radiations such as the X-rays used for radiation therapy or from the exposures received by the survivors the atomic bomb attacks in 1945. High LET data is harder to come by and derives largely from experiments using cells or animal model systems. These experiments use ground-based particle accelerators to accelerate ions to energies found in space and simulate potential space radiation exposures. Nearly all of this data come from experiments using a single ion at a solitary energy. As mentioned above, the space radiation environment is far more complex with many ions traveling with large ranges of energies all of which could impact an astronaut’s health, particularly since the probability of a cell in an astronaut’s body being hit sequentially by a small number of different ion species over a Mars mission lasting 600 to 900 days is quite high. In order to provide more realistic simulations of the space radiation environment, NASA is developing the GCR Simulator which has the potential to irradiate samples with multiple ion species within the shortest period of time allowed by ion switching, in order to mimic the effects of coincident (simultaneous) exposure. For the GCR simulator to best duplicate the natural space radiation environment, it is important to optimize dose delivery in ways that allow the results to be directly scalable to the low doses and dose rates that are encountered in deep space.

It will be difficult to match the low doses and dose rates directly. From a practical sense higher doses will need to be used in order to obtain statistically meaningful results. Likewise, higher dose rates are also required as exposing samples over long periods of time is just not feasible. Classically, the dose problem has been resolved by exposing samples to a series of higher doses then extrapolating the results back to the doses of interest. Similarly, it has long been known that as the dose rate declines the yield of biological endpoints is also diminished. This diminishment, however, only occurs to a point beyond which no additional decline in the dose response is detectable. The dose rate at which this point occurs has been termed the limiting low dose rate (LLDR). We plan to determine the LLDR for chromosome aberration induction by first measuring the dose response at high dose rate then using a mathematical model estimate the LLDR. The derived value for the LLDR will be tested in subsequent experiments. If we have achieved the LLDR the dose response will be strictly linear making extrapolations back to the conditions in the space radiation environment relatively straightforward. Future experiment will determine how best to fractionate the dose (deliver the dose in small increments with periods of time between each exposure) in a way that will achieve the same result as a continuous low dose rate exposure.

This is the first year for our project. As scheduling beam time at the NASA Space Radiation Laboratory (NSRL) is a somewhat long and involved process, we applied for time at the earliest opportunity after funding was secured. At present, our experiments have yet to run but our first run at NSRL is scheduled for April 11, 2019 using 250 MeV/n Helium ions. This is to be followed by a second experiment using 1 GeV protons on April 15. With this in mind, we have not yet been able to produce any results so far but hope to have our initial high dose rate experiments completed in the next few months.

One strategy to avoid track interactions is to lower the dose rate. By spacing out the time over which ions pass through a cell, breaks forming early in the time frame have an opportunity to be repaired before other breaks forming spatially close enough to interact with them arrive on the scene. This produces a reduction in the frequency of chromosome exchanges. As the dose rate decreases further a point is reached where virtually all the exchanges result from single track action. At this “limiting low dose rate” no additional reduction in chromosome exchange frequency is possible by further reduction in the dose rate. These results will be directly scalable to the low doses and dose rates present in space. Specific aim 1 of our proposal will endeavor to determine the limiting low dose rate for protons at the energy stated in the NRA (NASA Research Announcement). This will be accomplished by irradiating cells with a series of doses at dose rates we estimate will be close to the limiting low dose rate and looking for chromosome exchanges. When additional reduction in doses rate fails to produce any further decrease in exchanges as a function of dose we will be at the limiting low dose rate.

The GCR simulator will be irradiating samples with a number of different ion beams in order to better simulate the nature of the mixed ion field found in space. The heavier ions in the GCR spectrum will behave differently from the lighter ions. The heavy ions produce more damage along their tracks--so much so that virtually all chromosome exchanges are formed via single track action. In this case we will need to determine the optimal time needed for repair to occur between irradiations with the subsequent ion beams to avoid track interaction. Specific aim 2 will address these concerns by varying the time between ion beams. Much like the dose rate experiments, as we extend the time between irradiations, the probability for track interaction should be reduced. Once we reach a level where no further chromosome exchange frequency reductions are observed, we will have reached the optimal point for irradiation delay. Sequence may also be important in that regard and additional experiment will search for the best sequence that minimizes track interaction.