The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters ²²³Ra, ¹⁸⁸Re, and ^99mTc

Abstract

Background

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). 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).

Methods

Radioactive 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.

Results

Exposure 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.

Conclusions

For 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 material

The online version of this article (doi:10.1186/s13550-016-0203-x) contains supplementary material, which is available to authorized users.