Abstract
BackgroundDNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by 223Ra compared to 188Re and 99mTc modulated by the radical scavenger dimethyl sulfoxide (DMSO).MethodsRadioactive solutions of 223Ra, 188Re, or 99mTc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay.ResultsExposure to 120 Gy of 223Ra, 188Re, or 99mTc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy 223Ra and 500 Gy 188Re or 99mTc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter 223Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with 223Ra, 188Re, and 99mTc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for 223Ra, 188Re, and 99mTc, respectively.ConclusionsFor 223Ra, as well as for 188Re and 99mTc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-016-0203-x) contains supplementary material, which is available to authorized users.
Highlights
DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation
To elucidate the contrary findings regarding the effects from high linear energy transfer (LET) emitters, we studied the DNA damage and reduction of cellular survival induced by α-particles from 223Ra in comparison to β-and Auger electron emitters
Comparison of the effects in plasmid DNA and PC Cl3 cells Regarding the two biological systems, we found that dimethyl sulfoxide (DMSO) could diminish DNA damage in a similar manner for each of the radiation sources, as shown in Figs. 1 and 4
Summary
DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). The molecular nature of DNA damage is characterized by the physical properties of energy deposition and the chemical environment. The dependence on these parameters can be evaluated using simple experimental systems that allow the quantification of DNA damage. As underlined by several studies, the severity of the DNA damage depends on the linear energy transfer (LET) of the radiation quality [8,9,10]. DNA damage in plasmid DNA and cells by α-particles is assumed to be only partly protectable by DMSO due to the decreased role of the free radical processes [2, 9, 11]
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