ANALYSIS OF THE LETHAL EFFECTS OF LOW-DOSE RADIATION ON GLIOMA CELLS: RELATIONSHIP OF THE BYSTANDER EFFECT AND METAL ELEMENTS

Investigation of the radiation-induced bystander effect plays an important role in the understanding of the mechanisms of radiation response after low-dose irradiation. Sphingomyelinase (SMase) was activated by radiation and required the metal element for its activation. For further elucidation of the bystander effect, we investigated the relationship between its induction by acid SMase and a factor secreted from the irradiated tumor cells. In the cell culture medium transfer experiment after irradiation at a dose of 0.1 Gy, cell death was induced in non-irradiated cells. However, when cells received prior treatment with SMase inhibitor, cell death was not induced. When fluctuations in the activation of SMase and metal elements were detected, both intracellularly and extracellularly after irradiation, an increase in SMase activity and Zn concentration occurred within the cells at 5 min and outside of the cells at 15 min after irradiation. This increase in zinc concentration at 15 min after irradiation was suppressed by treatment with SMase inhibitor. These results suggest that activation of SMase, which is related to the bystander effect, is dependent on zinc.