N. F. Metting

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.

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.

Kinetic Differences Between Fed and Starved Chinese Hamster Ovary Cells

When Chinese hamster (CHO‐K1) cells are grown as monolayer cultures, they eventually reach a population‐density plateau after which no net increase in cell numbers occurs. the kinetics of aged cells in nutritionally deprived (starved) or density‐inhibited (fed) late plateau‐phase cultures were studied by four methods: (i) Reproductive integrity and cell viability were monitored daily by clonogenic‐cell assay and erythrosin‐b dye‐exclusion techniques. (ii) Mitotic frequencies of cells from 18 day old cultures were determined during regrowth by analysing time‐lapse video microscope records of dividing cells. (iii) Tritiated‐thymidine ([3H]TdR) auto‐radiography was used to determine the fractions of DNA‐synthesizing cells in cultures entering plateau phase and during regrowth after harvest. (iv) the rate of labelled nucleoside uptake and incorporation into DNA was measured using liquid scintillation or sodium iodide crystal counters after labelling with [3H]TdR or [125]UdR.

Low Dose Radiation Epidemiology: What Can It Tell Us?

A small workshop entitled ‘‘Low Dose Radiation Epidemiology—What Can it Tell Us?’’ was held at the North Bethesda Marriott Hotel, December 10–11, 2008. The workshop was organized and funded by the Department of Energy’s Low Dose Radiation Research Program, and the Organizing Committee consisted of a member each from DOE, EPA and NCI, plus one member from an academic institution. Participants were chosen for their acknowledged expertise and included 29 epidemiologists, four dosimetrists, and five radiation biologists. The impetus for holding the workshop was the following: There is some suggestion from research in cellular and animal systems that the biological response may differ after highand low-dose/dose-rate radiation exposure. There is no consensus, however, as to whether these differences would result in higher or lower risks of cancer or other diseases than would be predicted from the linear extrapolation defined by current epidemiological data. The workshop participants discussed the value of current human epidemiological data at lower doses and the possibilities for improving and expanding lowdose data obtained from epidemiological studies. On the first day, the selected existing epidemiological studies of low-dose/low-dose-rate exposed populations were reviewed.

Interpreting Survival Observations Using Phenomenological Models

It is generally accepted that the dose-rate dependence of the mammalian-cell survival curve reflects the modification of initial damage by cellular biochemical processes. However, these processes have not been adequately described to allow predictions of the effects at low doses or of radiations having higher stopping powers. The kinetics of damage induction and removal have been studied extensively, even though specific mechanisms have yet to be demonstrated. For example, it can be shown that one component of cell killing depends on the square of the concentration of radiation damage, a dependence that can be explained by sublethal damage models as well as by models featuring misrepair of potentially lethal damage. We have demonstrated two components of radiation-damage repair in plateau-phase Chinese hamster ovary cells. Analysis of repair rates shows that one component has a mean repair time of less than 1 hour, and another has a time of 18 hours. Repair rates, and fractions of damage repaired, appear independent of the initial amounts of damage produced. We have compared our data with the predictions of several different phenomenological models. These observations do not appear compatible with simple models that assume either the saturation of a rapid repair process or the interaction of pairs of sublesions. Rather, they support more-complex models that consider combinations of both sublethal and potentially lethal damage or multiple-step processes. Our observations are also consistent with models that consider the accessibility of damage to the repair enzymes.