Dose-Rate Effects of Protons and Light Ions for DNA Damage Induction, Survival and Transformation in Apparently Normal Primary Human Fibroblasts

We report on effects of low-dose exposures of accelerated protons delivered at high-dose rate (HDR) or a simulated solar-particle event (SPE) like low-dose rate (LDR) on immediate DNA damage induction and processing, survival and in vitro transformation of low passage NFF28 apparently normal primary human fibroblasts. Cultures were exposed to 50, 100 and 1,000 MeV monoenergetic protons in the Bragg entrance/plateau region and cesium-137 γ rays at 20 Gy/h (HDR) or 1 Gy/h (LDR). DNA double-strand breaks (DSB) and clustered DNA damages (containing oxypurines and abasic sites) were measured using transverse alternating gel electrophoresis (TAFE) and immunocytochemical detection/scoring of colocalized γ-H2AX pS139/53BP1 foci, with their induction being linear energy transfer (LET) dependent and dose-rate sparing observed for the different damage classes. Relative biological effectiveness (RBE) values for cell survival after proton irradiation at both dose-rates ranged from 0.61–0.73. Transformation RBE values were dose-rate dependent, ranging from ∼1.8–3.1 and ∼0.6–1.0 at low doses (≤30 cGy) for HDR and LDR irradiations, respectively. However peak transformation frequencies were significantly higher (1.3–7.3-fold) for higher doses of 0.5–1 Gy delivered at SPE-like LDR. Cell survival and transformation frequencies measured after low-dose 500 MeV/n He-4, 290 MeV/n C-12 and 600 MeV/n Si-28 ion irradiations also showed an inverse dose-rate effect for transformation at SPE-like LDR. This work demonstrates the existence of inverse dose-rate effects for proton and light-ion-induced postirradiation cell survival and in vitro transformation for space mission-relevant doses and dose rates.

On the choice of methodology for evaluating dose-rate effects on radiation-related cancer risks

Recently, several compilations of individual radiation epidemiology study results have aimed to obtain direct evidence on the magnitudes of dose-rate effects on radiation-related cancer risks. These compilations have relied on meta-analyses of ratios of risks from low dose-rate studies and matched risks from the solid cancer Excess Relative Risk models fitted to the acutely exposed Japanese A-bomb cohort. The purpose here is to demonstrate how choices of methodology for evaluating dose-rate effects on radiation-related cancer risks may influence the results reported for dose-rate effects. The current analysis is intended to address methodological issues and does not imply that the authors recommend a particular value for the dose and dose-rate effectiveness factor. A set of 22 results from one recent published study has been adopted here as a test set of data for applying the many different methods described here, that nearly all produced highly consistent results. Some recently voiced concerns, involving the recalling of the well-known theoretical point—the ratio of two normal random variables has a theoretically unbounded variance—that could potentially cause issues, are shown to be unfounded when aimed at the published work cited and examined in detail here. In the calculation of dose-rate effects for radiation protection purposes, it is recommended that meta-estimators should retain the full epidemiological and dosimetric matching information between the risks from the individual low dose-rate studies and the acutely exposed A-bomb cohort and that a regression approach can be considered as a useful alternative to current approaches.

High-dose-rate effects in the radiolysis of water at elevated temperatures.

Monte Carlo track chemistry simulations were used to study the effects of high dose rates on the radical (e-aq, H•, and •OH) and molecular (H2 and H2O2) yields in the low linear energy transfer (LET) radiolysis of liquid water at elevated temperatures between 25–350 °C. Our simulation model consisted of randomly irradiating water by single pulses of N incident protons of 300 MeV (LET ~ 0.3 keV/μm), which penetrate at the same time perpendicular to this water within the surface of a circle. The effect of dose rate was studied by varying N. Our simulations showed that, at any given temperature, the radical products decrease with increasing dose rate and, at the same time, the molecular products increase, resulting from an increase in the inter-track, radical-radical reactions. Using the kinetics of the decay of hydrated electrons at 25 and 350 °C, we determined a critical time (τc) for each value of N, which corresponds to the “onset” of dose-rate effects. For our irradiation model, τc was inversely proportional to N for the two temperatures considered, with τc at 350 °C being shifted by an order of magnitude to shorter times compared to its values at 25 °C. Finally, the data obtained from the simulations for N = 2,000 generally agreed with the observation that during the track stage of the radiolysis, free radical yields increase, while molecular products decrease with increasing temperature from 25 to 350 °C. The exceptions of e-aq and H2 to this general pattern are briefly discussed.