DNA double-strand breaks (DSB) are among the most harmful DNA lesions induced by ionizing radiation (IR). Although the induction and repair of radiation-induced DSB is well studied for acute irradiation, responses to DSB produced by chronic IR exposures are poorly understood, especially in human stem cells. The aim of this study was to examine the formation of DSB markers (γH2AX and phosphorylated kinase ATM, pATM, foci) in human mesenchymal stem cells (MSCs) exposed to chronic gamma-radiation (0.1 mGy/min) in comparison with acute irradiation (30 mGy/min) at cumulative doses of 30, 100, 160, 240 and 300 mGy. A linear dose-dependent increase in the number of both γH2AX and pATM foci, as well as co-localized γH2AX/pATM foci (“true” DSB), were observed after an acute radiation exposure. In contrast, the response of MSCs to a chronic low dose-rate IR exposure deviated from linearity towards a threshold model, for γH2AX, pATM foci and γH2AX/pATM foci, with an indication of a “plateau”. The state of equilibrium between newly formed DSB at a low rate during the protracted exposure time and the elimination of a fraction of DSB is proposed as a mechanistic explanation of the non-linear DSB responses following a low dose-rate irradiation. This notion is supported by the observation of the elimination of a substantial fraction of DSB 6 h after the cessation of the exposures. Our results demonstrate non-linear dose responses for γH2AX and pATM foci in human MSCs exposed to low dose-rate IR and showed the existence of a threshold, which may have implications for radiation protection in humans.

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Abstract. The aim of this work is to develop methods for an assessment of critical doses and dose rates that can result in significant radiation-induced effects in agrocenoses. This is realized on an example of cultivated plants which are one of the main components of agroecosystems. Available information on dose dependences in such umbrella endpoints as reproduction, survival, morbidity, alterations in morphological and biochemical processes, genetic effects in crops, vegetables, fruit trees, etc are gathered from papers issued mainly in Russian scientific press during last 50 years. Data are maintained as database in MS Access that contains about 10000 records at the moment. As critical exposure values, doses are considered producing 50% changes of biological effect at acute impact (ED 50 ), or dose rates resulting in 10% changes at chronic exposure of plants (EDR 10 ). The critical doses and dose rates for agrocenosis estimated from available information on reproduction and survival are presented here. Primary data are assesed for their quality according to several criteria. Three models (linear, logariphmic, logistic) for dose-effect relationship are tested for an applicability to fit a dose-effect dependence taking account of their goodness-of-fit and robustness of ED 50 and EDR 10 estimates.

The basis for the use of protons for radiation therapy tasks is a fixed conventional value of their relative biological efficiency equal to 1,1. Numerous studies have showed that RBE of proton radiation is not a constant value and depends on a number of factors. The purpose of this study was to determine RBE of a thin scanning proton beam at the center of the distributed Bragg peak in experiments on the culture of murine B-16 melanoma cells. The cell suspension was irradiated in an aqueous phantom by a horizontal proton beam from three directions (0,90 and 180°) in doses from 2 to 8 Gy. Modulation of the energy of proton radiation was 47,5÷92,0 MeV. RBE protons were determined from the clonogenic activity of the cells compared with 60Co gamma quanta. A linear-quadratic model was used to construct the dose dependencies. Obtained RBE values of proton radiation (LET 3÷8 keV/μm) differed in the big party from the generally accepted value and was at the level of 10% survival rate of 1.5. The results obtained generally coincided with data of foreign authors performed on different facilities.

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