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Studying in vivo radiobiological effects using zebrafish embryos

Rescue effects

Rescue effect is closely related to a more extensively studied non-targeted effect of ionizing radiation known as radiation-induced bystander effect (RIBE), which was first observed in in vitro experiments. RIBE in cells referred to the phenomenon that unirradiated cells responded as if they had been irradiated after they had partnered with the irradiated cells or after they had been treated with the medium previously conditioning the irradiated cells. To date, two mechanisms underlying RIBE have been widely accepted, namely, (1) gap junction intercellular communication (GJIC) in the presence of physical contacts among the cells, and (2) communication of soluble signal factors among the cells through the shared medium. Various soluble signal factors that participate in RIBE have been proposed, including tumor necrosis factor-a (TNF-a), transforming growth factor-b1 (TGF-b1), interleukin-6 (IL-6), interleukin-8 (IL-8), nitric oxide (NO) and reactive oxygen species (ROS).

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The rescue effect describes the phenomenon where irradiated cells or irradiated organisms derive benefits from the feedback signals released from the bystander unirradiated cells or organisms. An example of the benefit is the mitigation of radiation induced DNA damages. Our group [1] discovered the rescue effect where the bystander cells, through sending intercellular feedback signals to the irradiated cells, mitigated the effects originally induced in the irradiated cells directly by the radiation. We [1] found that the rescue effect reduced (1) the DNA double strand breaks (DSBs) surrogated by the numbers of p53-binding protein 1 (53BP1) foci, (2) the genomic instability surrogated by the number of micronucleus (MN) formation, and (3) extent of apoptosis in the irradiated cells. In particular, we also revealed that unirradiated normal cells could rescue irradiated cancer cells.

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[1] Chen, S., Zhao, Y., Han, W., Chiu, S.K., Zhu, L., Wu, L., Yu, K.N., 2010. Rescue effects in radiobiology: unirradiated bystander cells assist irradiated cells through intercellular signal feedback. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 706, 59-64.

Publications on rescue effect

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(By our group)

• Chen, S., Zhao, Y., Han, W., Chiu, S.K., Zhu, L., Wu, L., Yu, K.N., 2010. Rescue effects in radiobiology: unirradiated bystander cells assist irradiated cells through intercellular signal feedback. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 706, 59-64. 
• Lam, R.K.K., Fung, Y.K., Han, W., Yu, K.N., 2015. Rescue effects: Irradiated cells helped by unirradiated bystander cells. International Journal of Molecular Sciences 16, 2591-2609. (Invited review paper)
• Lam, R.K.K., Han, W., Yu, K.N., 2015. Unirradiated cells rescue cells exposed to ionizing radiation: Activation of NF-kB pathway in irradiated cells. Mutation Research 782, 23-33.
• Lam, R.K.K., Fung, Y.K., Han, W., Li, L., Chiu, S.K., Cheng, S.H., Yu, K.N., 2015. Modulation of NF-kB in rescued irradiated cells. Radiation Protection Dosimetry, 167, 37-43.

(By other groups)

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1. Widel, M., Przybyszewski, W.M., Cieslar-Pobuda, A., Saenko, Y.V., Rzeszowska-Wolny, J. 2012. Bystander normal human fibroblasts reduce damage response in radiation targeted cancer cells through intercellular ROS level modulation. Mutation Research 731, 117-124.

2. Pereira, S., Malard, V., Ravanat, J.-L., Davin, A.-H., Armengaud, J., Foray, N., Adam-Guillermin, C., 2914, Low doses of gamma-irradiation induce an early bystander effect in zebrafish cells which is sufficient to radioprotect cells. PLoS ONE 9, e92974.

3. Desai, S., Kobayashi, A., Konishi, T., Oikawa, M., Pandey, B.N., 2014. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation. Mutation Research 763-764, 39-44.

4. He, M., Dong, C., Xie, Y., Li, J., Yuan, D., Bai, Y., Shao, C., 2014. Reciprocal bystander effect between a-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway. Mutation Research 763-764, 1-9.

5. Widel, M., Lalik, A., Krzywon, A., Poleszczuk, J., Fujarewicz, K., Rzeszowska-Wolny, J., 2015. The different radiation response and radiation-induced bystander effects in colorectal carcinoma cells differing in p53 status. Mutation Research 778, 61-70.

6. Liu, Y., Kobayashi, A., Fu, Q., Yang, G., Konishi, T., Uchihori, Y., Hei, T.K., Wang, Y., 2015. Rescue of Targeted Nonstem-Like Cells from Bystander Stem-Like Cells in Human Fibrosarcoma HT1080. Radiation Research 184, 334-340.

7. Fu, J., Yuan, D., Xiao, L., Tu, W., Dong, C., Liu, W., Shao, C., 2015. The crosstalk between a-irradiated Beas-2B cells and its bystander U937 cells through MAPK and NF-kB signaling pathways, Mutation Research (in press) http://dx.doi.org/10.1016/j.mrfmmm.2015.11.001

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Nuclear Radiation Unit
Department of Physics
City University of Hong Kong
Tat Chee Ave, Kowloon Tong, Hong Kong
Email: apnru@cityu.edu.hk

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