Bystander signal production and response are independent processes which are cell line dependent

Purpose: Radiation-induced bystander effects are now an established phenomenon seen in numerous models; however it is not known whether the magnitude of the bystander effect is determined by the signal produced by the irradiated cells or the response of the exposed cells. The aim of this investigation is to determine the importance of the bystander signal versus the bystander response in three different cell line models. Methods: A matrix design experiment using cell lines, HPV-G, CHO-K1 and E89 (glucose 6-phosphate dehydrogenase (G6DP) null) was set up to produce irradiated cell conditioned medium (ICCM), which was used to treat all cell lines. Results: For HPV-G and CHO-K1 lines, the response to autologous ICCM was significantly different to that when treated with ICCM generated from another line. These lines displayed no response to E89 ICCM, nor did E89 cells show a significant response to any ICCM, suggesting that G6DP plays a key role in the bystander effect. Conclusion: These data suggest, for these cell lines at least, that in the case of cell lines capable of responding to the bystander signal, it is the signal produced by the irradiated cell that determines the magnitude of the bystander effect.