The impact of radiation-induced
bystander effect (RIBE) is still
not well understood in radiotherapy. RIBEs are biological effects
expressed by nonirradiated cells near or far from the irradiated cells.
Most radiological studies on cancer cells have been based on biochemical
characterization. However, biophysical investigation with label-free
techniques to analyze and compare the direct irradiation effect and
RIBE has lagged. In this work, we employed an electrical cell-indium
tin oxide (ITO) substrate impedance system (ECIIS) as a bioimpedance
sensor to evaluate the HeLa cells’ response. The bioimpedance
of untreated/nonirradiated HeLa (N-HeLa) cells, α-particle (Am-241)-irradiated
HeLa (I-HeLa) cells, and bystander HeLa (B-HeLa) cells exposed to
media from I-HeLa cells was monitored with a sampling interval of
8 s over a period of 24 h. Also, we imaged the cells at times where
impedance changes were observed. Different radiation doses (0.5 cGy,
1.2 cGy, and 1.7 cGy) were used to investigate I-HeLa and B-HeLa cells’
radiation-dose-dependence. By analyzing the changes in absolute impedance
and cell size/number with time, compared to N-HeLa cells, B-HeLa cells
mimicked the I-HeLa cells’ damage and modification of proliferation
rate. Contrary to the irradiated cells, the bystander cells’
damage rate and proliferation rate enhancements have an inverse radiation-dose-response.
Also, we report multiple RIBEs in HeLa cells in a single measurement
and provide crucial insights into the RIBE mechanism without any labeling
procedure. Unambiguously, our results have shown that the time-dependent
control of RIBE is important during α-radiation-based radiotherapy
of HeLa cells.