Suppressive effect of ascorbic acid on the mutagenesis induced by the bystander effect through mitochondrial function

Abstract

Here, we focused on suppressive effect of ascorbic acid (AsA) on changes in mitochondrial function and mutagenesis by the radiation- induced bystander effect (RIBE). In mammalian cell lines, medium transfer assay was performed and conditioned medium including secreted factors after X-irradiation were examined to detect the RIBE. We found that the membrane potential and increased levels of superoxide radical (O₂⁻) in mitochondria were modulated in cells treated with conditioned medium from irradiated cells. The result of the present study also demonstrated that increases in reactive oxygen species (ROS) levels led to the induction of gene mutations. Interestingly, the modulations in mitochondria, in addition to mutation inductions by RIBE, were completely suppressed by treatment with AsA in cells treated with conditioned medium. These results suggest that mutagenesis, which may have resulted from secreted factors involving the RIBE, may be induced by ROS that are localized in mitochondria and may be relieved by AsA.

Keywords::

• ionizing radiation
• bystander effect
• mitochondria
• mutagenesis
• ascorbic acid

Acknowledgements

We appreciate Dr Masayuki Seki and Mr Yoshifumi Hosono (Tohoku University) for their kind gift, HA-SOD2 plasmid.

Declaration of interest

The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.

This work was supported by grants for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology-Japan (21791190, 24791317) and for The Nuclear Safety Research Enhancement Actions from the Nuclear Safety Commission of Japan.