Rescue Effects: Irradiated Cells Helped by Unirradiated Bystander Cells

Abstract

The rescue effect describes the phenomenon where irradiated cells or organisms derive benefits from the feedback signals sent from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation-induced DNA damages in the irradiated cells. The rescue effect can compromise the efficacy of radioimmunotherapy (RIT) (and actually all radiotherapy). In this paper, the discovery and subsequent confirmation studies on the rescue effect were reviewed. The mechanisms and the chemical messengers responsible for the rescue effect studied to date were summarized. The rescue effect between irradiated and bystander unirradiated zebrafish embryos in vivo sharing the same medium was also described. In the discussion section, the mechanism proposed for the rescue effect involving activation of the nuclear factor κB (NF-κB) pathway was scrutinized. This mechanism could explain the promotion of cellular survival and correct repair of DNA damage, dependence on cyclic adenosine monophosphate (cAMP) and modulation of intracellular reactive oxygen species (ROS) level in irradiated cells. Exploitation of the NF-κB pathway to improve the effectiveness of RIT was proposed. Finally, the possibility of using zebrafish embryos as the model to study the efficacy of RIT in treating solid tumors was also discussed.

The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status

“…The bystander effect is a phenomenon not only of the impact of irradiated cells on non-irradiated cells, but also an inverse communication which often takes the nature of rescue signaling [78]. Since the level of IL-6 decrease in co-culture media in comparison with that without co-culture, it is also possible that molecules of IL-6 are captured by the soluble receptors for IL-6.…”

A correlation of long term effects and radiation quality in the progeny of bystander cells after microbeam radiations: The experimental study of radiotherapy for cancer risk mitigation

“…Futuremore, the progeny of bystander cells that undergo genomic instability and cancer development greatly depend on the quality of radiation, induction of mutation, oxidative stress and other, especially in the high-LET radiation where small effects are expected [26][27]. …”

Effects of photon hormesis on cells irradiated by alpha particles

“…If we adopt that the average area of an HCT116 cell is 266 m 2 [20], each cell will be on average hit by about 7 alpha particles. As such, we do not need to consider the complications brought about by the radiation-induced bystander effect [21][22][23] or the rescue effect [17,24]. Figure 2 shows the responses (in terms of numbers of 53BP1 fpc) of WT and p53-/-HCT116 cells in both IA and IAX groups at different time points.…”