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Studying in vivo radiobiological effects using zebrafish embryos

An adult zebrafish, Danio rerio.

In recent years, the zebrafish, Danio rerio, a small vertebrate from Southeast Asia, has become a preferred model for studying human disease, including carcinogenesis. The most important advantage is that the human and zebrafish genomes share considerable homology, including conservation of most DNA repair-related genes. Rapid embryonic development is another advantage so the effects can be assessed within 24 hours post fertilization (hpf). We began using zebrafish embryos to study in vivo radiobiological effects in 2007 [1]. The studied in vivo radiobiological effects include the hormetic effect, adaptive response, bystander effect, rescue effect and multiple stressor effect. A recent review on using zebrafish embryos to study non-targeted effects of ionizing radiation can be found in Ref. [2].

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References

[1] Yum, E.H.W., Ng, C.K.M., Lin, A.C.C., Cheng, S.H., Yu, K.N., 2007. Experimental setup for studying the effects of alpha particles on zebrafish embryos. Nuclear Instruments and Methods in Physics Research B, 264, 171-176.

[2] Choi, V.W.Y., Yu, K.N. 2015. Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation. Cancer Letters 356, 91-104.

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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).

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.

[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.

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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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