Speaker
Prof.
Andreyan Osipov
(Burnazyan Federal Medical Biophysical Center of the Federal Medical-Biological Agency)
Description
There is a considerable controversy as to whether DNA damage induced by low doses and low dose rates of ionizing radiation is treated similarly by cellular defence machineries and what downstream delayed effects it causes compared to moderate to high doses. This constitutes the major challenge for the linear no-threshold model (LNT) currently used for radiological risk estimates. Among various DNA lesions induced by ionizing radiation DNA double strand breaks (DSBs) are of the most importance due to their potential to cause cell death, mutagenesis and carcinogenesis. The aim of this study was to examine accumulation of DNA DSBs in mouse blood leucocytes and splenocytes upon in vivo long-term chronic low dose gamma-irradiation. Animals were irradiated for 40, 80 or 120 days at a dose rate of 0.15 mGy/h, with total accumulated doses being 144, 288 and 432 mGy, respectively. DNA DSBs were measured in blood leucocytes and splenocytes using neutral comet assay. At the first time-point of 40 days we observed a slightly increased DSBs levels in exposed animals compared to control ones. Continuation of the exposure up to 80 days lead to a surprising finding that the DSB levels in the irradiated animals dropped below the control level. By day 120 of the irradiation, we still observed lower levels of DSBs in cells from exposed animals compared to unexposed controls, although the difference started to diminish. The effect at later times of irradiation could be explained based on the suggested inducibility of the DNA repair, once the threshold for signaling has been reached. We could further speculate that other mechanisms may be involved, such as the elimination of a hypersensitive and/or damaged sub-population of cells (e.g. by immune system). The question of whether low levels of DNA damage from low dose/dose rate exposures are dealt with by molecular repair systems in the same way as in the case of high dose exposures has a direct implication for radiological protection. This is due to a significant role played by cellular genome integrity machineries in carcinogenesis, with cancer being the most significant and formally accepted health consequence of ionizing radiation. Current LNT model used by authorities to calculate and control radiological risks has been largely criticized and debated. Our results provide further support for non-linearity in biological effects of low dose radiation, now at a molecular level of primary DNA lesions.
Primary author
Prof.
Andreyan Osipov
(Burnazyan Federal Medical Biophysical Center of the Federal Medical-Biological Agency)
Co-authors
Dr
Dmitry Klokov
(Chalk River Laboratories, Atomic Energy of Canada Limited)
Dr
Ekaterina Lizunova
(Semenov Institute of Chemical Physics of Russian Academy of Sciences)
Mrs
Galina Buleeva
(Semenov Institute of Chemical Physics of Russian Academy of Sciences)
