L.A. Braby

Opportunities for nutritional amelioration of radiation-induced cellular damage

The closed environment and limited evasive capabilities inherent in space flight cause astronauts to be exposed to many potential harmful agents (chemical contaminants in the environment and cosmic radiation exposure). Current power systems used to achieve space flight are prohibitively expensive for supporting the weight requirements to fully shield astronauts from cosmic radiation. Therefore, radiation poses a major, currently unresolvable risk for astronauts, especially for long-duration space flights. The major detrimental radiation effects that are of primary concern for long-duration space flights are damage to the lens of the eye, damage to the immune system, damage to the central nervous system, and cancer. In addition to the direct damage to biological molecules in cells, radiation exposure induces oxidative damage. Many natural antioxidants, whether consumed before or after radiation exposure, are able to confer some level of radioprotection. In addition to achieving beneficial effects from long-known antioxidants such as vitamins E and C and folic acid, some protection is conferred by several recently discovered antioxidant molecules, such as flavonoids, epigallocatechin, and other polyphenols. Somewhat counterintuitive is the protection provided by diets containing elevated levels of omega-3 polyunsaturated fatty acids, considering they are thought to be prone to peroxidation. Even with the information we have at our disposal, it will be difficult to predict the types of dietary modifications that can best reduce the risk of radiation exposure to astronauts, those living on Earth, or those enduring diagnostic or therapeutic radiation exposure. Much more work must be done in humans, whether on Earth or, preferably, in space, before we are able to make concrete recommendations.

Relative Effectiveness of HZE Iron-56 Particles for the Induction of Cytogenetic Damage In Vivo

Abstract Brooks, A. L., Bao, S., Rithidech, K., Couch, L. A. and Braby, L. A. Relative Effectiveness of HZE Iron-56 Particles for the Induction of Cytogenetic Damage In Vivo. One of the risks of prolonged manned space flight is the exposure of astronauts to radiation from galactic cosmic rays, which contain heavy ions such as 56Fe. To study the effects of such exposures, experiments were conducted at the Brookhaven National Laboratory by exposing Wistar rats to high-mass, high-Z, high-energy (HZE) particles using the Alternating Gradient Synchrotron (AGS). The biological effectiveness of 56Fe ions (1000 MeV/nucleon) relative to low-LET γ rays and high-LET α particles for the induction of chromosome damage and micronuclei was determined. The mitotic index and the frequency of chromosome aberrations were evaluated in bone marrow cells, and the frequency of micronuclei was measured in cells isolated from the trachea and the deep lung. A marked delay in the entry of cells into mitosis was induced in the bone marrow cells that decreased as a function of time after the exposure. The frequencies of chromatid aberrations and micronuclei increased as linear functions of dose. The frequency of chromosome aberrations induced by HZE particles was about 3.2 times higher than that observed after exposure to 60Co γ rays. The frequency of micronuclei in rat lung fibroblasts, lung epithelial cells, and tracheal epithelial cells increased linearly, with slopes of 7 × 10−4, 12 × 10−4, and 11 × 10−4 micronuclei/binucleated cell cGy−1, respectively. When genetic damage induced by radiation from 56Fe ions was compared to that from exposure to 60Co γ rays, 56Fe-ion radiation was between 0.9 and 3.3 times more effective than 60Co γ rays. However, the HZE-particle exposures were only 10–20% as effective as radon in producing micronuclei in either deep lung or tracheal epithelial cells. Using microdosimetric techniques, we estimated that 32 cells were hit by δ rays for each cell that was traversed by the primary HZE 56Fe particle. These calculations and the observed low relative effectiveness of the exposure to HZE particles suggest that at least part of the cytogenetic damage measured was caused by the δ rays. Much of the energy deposited by the primary HZE particles may result in cell killing and may therefore be “wasted” as far as production of detectable micronuclei is concerned. The role of wasted energy in studies of cancer induction may be important in risk estimates for exposure to HZE particles.

Microdosimetry near the Trajectory of High-Energy Heavy Ions

Single-event energy distributions were measured in a 1.3-micron-diameter site as a function of radial distance from the trajectory of high-energy iron ions having an energy of about 600 MeV/amu. It was found that beyond distances of a few micrometers the average lineal energy of the (mostly single) secondary electrons (delta rays) is of the order of 3 keV/micron. This is similar to the value found in a medium irradiated by 170-keV photons. The frequency-mean specific energy for delta rays occurring at large distances from the path of the primary ion exceeds the calculated (radial) absorbed dose by two orders of magnitude.

Clastogenic effects of defined numbers of 3.2 MeV alpha particles on individual CHO-K1 cells

Research to determine the effects of defined numbers of alpha particles on individual mammalian cells is helpful in understanding risks associated with exposure to radon. This paper reports the first biological data generated using the single-particle/single-cell irradiation system developed at Pacific Northwest Laboratory. Using this apparatus, CHO-K1 cells were exposed to controlled numbers of 3.2 MeV alpha particles, and biological responses of individual cells to these irradiations were quantified. Chromosomal damage, measured by the induction of micronuclei, was evaluated after no, one, two, three or five particle traversals. Exposures of up to five alpha particles had no influence on the total numbers of cells recovered for scoring. With increased numbers of alpha particles there was a decrease in the ratio of binucleated to mononucleated cells of 3.5%/hit, suggesting that alpha particles induced dose-dependent mitotic delay. A linear hit-response relationship was observed for micronucleus induction: Micronuclei/binucleated cell = 0.013 +/- 0.036 + (0.08 +/- 0.013) x D, where D is the number of particles. When the estimated dose per alpha-particle traversal was related to the frequency of induced micronuclei, the amount of chromosomal damage per unit dose was found to be similar to that resulting from exposures to alpha particles from other types of sources. Approximately 72% of the cells exposed to five alpha particles yield no micronuclei, suggesting the potential for differential sensitivity in the cell population. Additional studies are needed to control biological variables such as stage of the cell cycle and physical parameters to ensure that each cell scored received the same number of nuclear traversals.

Recent space shuttle observations of the South Atlantic anomaly and the radiation belt models

Active instruments consisting of a tissue equivalent proportional counter (TEPC) and a proton and heavy ion detector (PHIDE) have been carried on a number of Space Shuttle flights. These instruments have allowed us to map out parts of the South Atlantic Particle Anomaly (SAA) and to compare some of its features with predictions of the AP-8 energetic proton flux models. We have observed that consistent with the generally observed westward drift of the surface features of the terrestrial magnetic field the SAA has moved west by about 6.9 degrees longitude between the epoch year 1970 of the AP-8 solar maximum model and the Space Shuttle observations made twenty years later. However, calculations indicate that except for relatively brief periods following very large magnetic storms the SAA seems to occupy the same position in L-space as in 1970. After the great storm of 24 March 1991 reconfiguration of the inner radiation belt and/or proton injection into the inner belt, a second energetic proton belt was observed to form at L approximately = 2. As confirmed by a subsequent flight observations, this belt was shown to persist at least for six months. Our measurements also indicate an upward shift in the L location of the primary belt from L = 1.4 to L = 1.5. In addition we confirm through direct real time observations the existence and the approximate magnitude of the East-West effect.

Dose-Rate Evidence for Two Kinds of Radiation Damage in Stationary-Phase Mammalian Cells

Survival based on colony formation was measured for starved plateau-phase Chinese hamster ovary (CHO) cells exposed to 250 kVp X rays at dose rates of 0.0031, 0.025, 0.18, 0.31, and 1.00 Gy/min. A large dose-rate effect was demonstrated. Delayed plating experiments and dose response experiments following a conditioning dose, both using a dose rate of 1.00 Gy/min and plating delays of up to 48 hr, were also used to investigate the alternative repair hypotheses. There is clearly a greater change in survival in dose-rate experiments than in the other experiments. Thus we believe that a process which depends on the square of the concentration of initial damage, and which alters the effect of initial damage on cell survival is being observed. We have applied the damage accumulation model to separate the single-event damage from this concentration-dependent form and estimate the repair rate for the latter type to be 70 min for our CHO cells. Use of this analysis on other published dose-rate studies also yields results consistent with this interpretation of the repair mechanisms.

Multiple components of split-dose repair in plateau-phase mammalian cells: a new challenge for phenomenological modelers.

Split-dose experiments using starved plateau-phase Chinese hamster ovary cells have been used to investigate the kinetics of repair, expressed in terms of enhancement of reproductive survival. The results show two distinct components of repair, one having a characteristic time of just over 1 h for the removal of a lesion, the other, about 18 h. The rate at which each component removes damage and the fraction of the total damage that each removes appear to be independent of the initial amount of damage produced, i.e., dose. This lack of dose dependence is not consistent with some simple models of ionizing radiation damage and repair, such as those which assume that saturation of a repair process, depletion of enzyme pools, or the interaction of pairs of sublesions is responsible for the curvature in the dose-response relationship. However, the relationship between the amounts of each type of damage and dose appears to be consistent with models that assume that only a portion of the initial damage is directly accessible to the repair systems or that the initial damage consists of a mixture of potentially lethal and sublethal lesions.

Cellular effects of individual high-linear energy transfer particles and implications for tissue response at low doses

The energy deposition patterns produced by the radiation environment in space can be quite different from those in conventional radiation environments. Furthermore, conventional radiation biological experiments, using randomly distributed particle tracks, cannot access some variables which may be important in determining the health effects of irradiation. Controlled microbeam irradiation provides the means to investigate the effects and unique energy deposition patterns and cell environment for a variety of end points.

Potential doses to passengers and crew of supersonic transports.

Data from a tissue equivalent proportional counter that was flown at altitudes ranging from 60,000 feet to 70,000 feet were used to estimate radiation quality factors at different latitudes. For high LET radiation, Q values of 11 to 14 were calculated for latitude 18 degrees north to 59 degrees north. Dose equivalent rates ranging from 5.2 microSv hr(-1) to 27 microSv hr(-1) were measured. These dose equivalent rates are about twice that computed using a computer code called CARI-4Q. The dose equivalent received during a flight from Los Angeles to Tokyo was computed using CARI-4Q and the result doubled, based on the TEPC to CARI-4Q ratio. Members of the general public, including frequent flyers, would not exceed dose limits recommended by the ICRP. Air crew would not exceed the limits for occupationally exposed persons. However, pregnant air crew, based on a 2 mSv limit to concepti, would exceed the limit after 150 hours flying time.

Response of a tissue equivalent proportional counter to neutrons

The absorbed dose as a function of lineal energy was measured at the CERN-EC Reference-field Facility (CERF) using a 512-channel tissue equivalent proportional counter (TEPC), and neutron dose equivalent response evaluated. Although there are some differences, the measured dose equivalent is in agreement with that measured by the 16-channel HANDI tissue equivalent counter. Comparison of TEPC measurements with those made by a silicon solid-state detector for low linear energy transfer particles produced by the same beam, is presented. The measurements show that about 4% of dose equivalent is delivered by particles heavier than protons generated in the conducting tissue equivalent plastic.