‘@

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 examined in vivo radiobiological effects include the hormetic effect, photon hormesis, adaptive response, rescue effect, bystander 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].

‘@

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.

‘@

‘@

‘@

Hormetic effect

Hormetic responses are characterized by biphasic dose-response relationships showing a low-dose stimulation and a high-dose inhibition. Alpha-particle-induced hormetic effect has been demonstrated in zebrafish embryos using alpha particles [1,2], and has been found to be communicated to bystander unirradiated zebrafish embryos [3]. A subhormetic zone was also found in microbeam-proton-irradiated zebrafish embryos [4,5], which together with the hormetic and toxic zones constituted the triphasic low-dose response in zebrafish embryos.

‘@

References

[1] Yum, E.H.W., Cheng, S.H., Yu, K.N., 2009. Zebrafish embryos for studying radiation response in vivo. Journal of Radiation Research, 50, Supplement A, A93.

[2] Yum, E.H.W., Li, V.W.T., Choi, V.W.Y., Cheng, S.H., Yu, K.N., 2010. Effects of alpha particles on zebrafish embryos. Applied Radiation and Isotopes, 68, 714-717.

[3] Choi, V.W.Y., Cheung, A.L.Y., Cheng, S.H., Yu, K.N., 2012. Hormetic effect induced by alpha-particle-induced stress communicated in vivo between zebrafish embryos. Environmental Science & Technology, 46, 11678−11683.

[4] Choi, V.W.Y., Yum, E.H.W., Konishi, T., Oikawa, M., Cheng, S.H., Yu, K.N., 2012. Triphasic low-dose response in zebrafish embryos irradiated by microbeam protons. Journal of Radiation Research 53, 475-481.

[5] Choi, V.W.Y., Ng, C.Y.P., Kobayashi, A., Konishi, T., Oikawa, M., Cheng, S.H., Yu, P.K.N. 2014. Response of 5 hpf zebrafish embryos to low-dose microbeam protons. Journal of Radiation Research, 2014, 55, i113.

‘@

‘@

‘@

Photon hormesis

Photon hormesis or photon radiation hormesis refers to the phenomenon where the biological effect of an ionizing radiation (other than photons) is suppressed by a simultaneous small photon radiation exposure. The proposed mechanisms underlying photon hormesis include high-fidelity DNA repair and removal of aberrant cells through apoptosis. Photon hormesis was shown in the dose response of zebrafish embryos to 2-MeV neutrons, which showed that the responses to neutron doses of 70 and 100 mGy (corresponding to photon dose contamination of 9.8 and 14 mGy, respectively) were significantly lower than expected [1]. We were the first group ever to observe neutron-induced bystander effect (NIBE). The NIBE was found between irradiated and unirradiated zebrafish embryos for a certain neutron-dose range (20 to 50 mGy) [2]. Non-induction of NIBE for neutron doses >50 mGy was attributed to photon hormesis (with corresponding photon doses > 7 mGy). More recently, we also revealed that priming neutron doses applied at 5 hpf could not induce radioadaptive response (RAR) against a challenging X-ray dose of 2 Gy applied at 10 hpf [3]. Non-induction of RAR on embryos having received 25, 50 and 100 mGy of neutron doses was explained by photon hormesis which mitigated neutron-induced damages. Separate experimental results were provided to verify that high-energy photons could disable RAR. Specifically, 5 or 10 mGy X-rays disabled the RAR induced by a priming dose of 0.88 mGy of alpha particles delivered to 5 hpf zebrafish embryos against a challenging dose of 2 Gy X-rays delivered to the embryos at 10 hpf. [3]

‘@

References

[1] Ng, C.Y.P., Kong, E.Y., Konishi, T., Kobayashi, A., Suya, N., Cheng, S.H., Yu, K.N., 2015. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility. Radiation Physics and Chemistry 114, 12-17.

[2] Ng, C.Y.P., Kong, E.Y., Kobayashi, A., Suya, N., Uchihori, Y., Cheng, S.H., Konishi, T., Yu, K.N., 2015. Neutron induced bystander effect among zebrafish embryos. Radiation Physics and Chemistry, 117, 153-159.

[3] Ng, C.Y.P., Kong, E.Y., Kobayashi, A., Suya, N., Uchihori, Y., Cheng, S.H., Konishi, T., Yu, K.N., 2015. Non-induction of radioadaptive response in zebrafish embryos by neutrons. Journal of Radiation Research, in press.

‘@

‘@

‘@

Adaptive response

Adaptive response (AR) or radioadaptive response (RAR) occur when a small preceding priming dose decreases the biological effectiveness of a subsequent large challenging dose. RAR has been demonstrated in zebrafish embryos using alpha particles [1,2], and has been found to be communicated to bystander unirradiated zebrafish embryos [3]. RAR was also induced in microbeam-proton-irradiated zebrafish embryos [4,5] through nitric-oxide dependent pathways [6] and was likely to involve de novo synthesis of factors [7].

‘@

References

[1] Choi, V.W.Y., Lam, R.K.K., Chong, E.Y.W., Cheng, S.H., Yu, K.N., 2010. Designing experimental setup and procedures for studying alpha-particle-induced adaptive response in zebrafish embryos in vivo. Nuclear Instruments and Methods in Physics Research B, 268 651-656.

[2] Choi, V.W.Y., Wong, M.Y.P., Cheng, S.H., Yu, K.N., 2011. Dosimetric study of radioadaptive response of zebrafish embryos using PADC-film substrates. Radiation Measurements 46, 1795-1798.

[3] Choi, V.W.Y., Cheng, S.H., Yu, K.N., 2010. Radioadaptive Response Induced by Alpha-Particle-Induced Stress Communicated in Vivo between Zebrafish Embryos. Environmental Science & Technology, 44, 8829-8834.

[4] Choi, V.W.Y., Konishi, T., Oikawa, M., Iso, H., Cheng, S.H., Yu, K.N., 2010. Adaptive response in zebrafish embryos induced using microbeam protons as priming dose and x-ray photons as challenging dose. Journal of Radiation Research 51, 657-664.

[5] Choi, V.W.Y., Konishi, T., Oikawa, M., Cheng, S.H., Yu, K.N., 2013. Threshold number of protons for inducing adaptive response in zebrafish embryos. Journal of Radiological Protection, 33, 91-100.

[6] Choi, V.W.Y., Ng, C.Y.P., Kobayashi, A., Konishi, T., Oikawa, M., Cheng, S.H., Yu, P.K.N. 2014. Roles of nitric oxide in adaptive response induced in zebrafish embryos in vivo by microbeam protons. Journal of Radiation Research, 2014, 55, i114.

[7] Choi, V.W.Y., Ng, C.Y.P., Kobayashi, A., Konishi, T., Oikawa, M., Cheng, S.H., Yu, P.K.N. 2014. Exogenous carbon monoxide suppresses adaptive response induced in zebrafish embryos in vivo by microbeam protons. Journal of Radiation Research, 2014, 55, i115.

‘@

‘@

‘@

Rescue effect

Rescue effects refer to the phenomenon in which the biological effects of the irradiated cells/organisms are mitigated by the bystander unirradiated cells/organisms. We reported data demonstrating that zebrafish embryos irradiated by alpha particles could release a stress signal into the water, which could be communicated to the unirradiated zebrafish embryos sharing the same water medium, and then these unirradiated zebrafish embryos could release a feedback stress signal back to the irradiated embryos to mitigate the radiation induced DNA damages in the latter [1]. Our results also showed that the strength of the rescue effect depended on the number of rescuing bystander unirradiated embryos [1]. In a latter study, we also demonstrated that the signals for bystander effect and rescue effect had the same function [2]. We also found that unirradiated zebrafish embryos need nitric oxide but not the nitric-oxide-induced damages to rescue alpha-particle irradiated zebrafish embryos [2].

‘@

References

[1] Choi, V.W.Y., Ng, C.Y.P., Cheng, S.H., Yu, K.N., 2012. a-Particle irradiated zebrafish embryos rescued by bystander unirradiated zebrafish embryos. Environmental Science & Technology, 46, 226-231.

[2] Kong, E.Y., Choi, V.W.Y., Cheng, S.H., Yu, K.N., 2014. Some properties of the signals involved in unirradiated zebrafish embryos rescuing a-particle irradiated zebrafish embryos. International Journal of Radiation Biology, 90, 1133-1142.

‘@

‘@

Bystander effect

Radiation-induced bystander effects (RIBE) in cells/organisms refer to biological effects that the unirradiated cells/organisms respond as if they have been irradiated, when they are put in contact with the irradiated cells/organisms or in the medium previously holding the irradiated cells/organisms. Alpha-particle-induced bystander effect has been demonstrated in zebrafish embryos using alpha particles [1], which was attenuated of in a carbon-monoxide-concentration dependent manner [2]. RIBE was also implied in the induction of hormetic effect and adaptive response in bystander embryos, and in the induction of the rescue effect in the irradiated embryos in the presence of bystander embryos. We also found bystander effect between embryos irradiated with high-dose X-rays and unirradiated embryos through nitric-oxide dependent pathways [3].

‘@

References

[1] Yum, E.H.W., Choi, V.W.Y., Nikezic, D., Li, V.W.T., Cheng, S.H., Yu, K.N., 2009. Alpha-particle-induced bystander effects between zebrafish embryos in vivo. Radiation Measurements, 44, 1077-1080.

[2] Choi, V.W.Y., Wong, M.Y.P., Cheng, S.H., Yu, K.N., 2012. Effects of Exogenous Carbon Monoxide on Radiation-Induced Bystander Effect in Zebrafish Embryos in vivo. Applied Radiation and Isotopes, 70, 1075-1079.

[3] Choi, V.W.Y., Ng, C.Y.P., Kobayashi, A., Konishi, T., Suya, N., Ishikawa, T., Cheng, S.H., Yu, K.N. Bystander Effect between Zebrafish Embryos in Vivo Induced by High-Dose X-rays. Environmental Science & Technology, 2013, 47, 6368-6376.

‘@

‘@

‘@

Multiple stressor effect

Multiple stressor effects are the resultant effects due to exposures to a mixture of environmental stressors, e.g., ionizing radiations, heavy metals, etc. Evidence showed that toxicity could be modified by simultaneous or sequential exposures to multiple environmental agents. We have studied the multiple stressor effects of alpha particles and cadmium (Cd) on zebrafish embryos. Antagonistic effects occurred for alpha-particle irradiation followed by Cd exposure [1] and also for Cd exposure followed by alpha-particle irradiation [2]. On the other hand, mostly additive and some synergistic effects occurred for simultaneous alpha-particle irradiation and Cd exposure [3]. More recently, we have studied the multiple stressor effects of alpha particles and depleted uranium (DU) on zebrafish embryos. Interestingly, DU changed the hormetic effect brought about by alpha-particle irradiation into an apparently toxic effect. This could be explained in terms of the promotion of early death of cells predisposed to spontaneous transformation by the small alpha-particle dose (i.e. hormetic effect) and the postponement of cell death upon DU exposure [4].

‘@

References

[1] Yu, K.N., Tung, M.M.T., Choi, V.W.Y., Cheng, S.H., 2012. Alpha radiation exposure decreases apoptotic cells in zebrafish embryos subsequently exposed to the chemical stressor, Cd. Environmental Science and Pollution Research, 19, 3831-3839.

[2] Choi, V.W.Y., Ng, C.Y.P., Kong, M.K.Y., Cheng, S.H., Yu, K.N., 2013. Adaptive response to ionizing radiation induced by cadmium in zebrafish embryos. Journal of Radiological Protection, 33, 101-112.

[3] Ng, C.Y.P., Choi, V.W.Y., Lam, A.C.L., Cheng, S.H., Yu, K.N., 2013. Multiple stressor effect in zebrafish embryos from simultaneous exposures to ionizing radiation and cadmium. Journal of Radiological Protection, 33, 113-121.

[4] Ng, C.Y.P., Pereira, S., Cheng, S.H., Adam-Guillermin, C., Garnier-Laplace, J., Yu, K.N., 2015. Combined effects of depleted uranium and ionising radiation on zebrafish embryos. Radiation Protection Dosimetry, 167, 311-315.

‘@

Rescue effects

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

Page last modified on 3-Jul-2017

Privacy Policy - Copyright - Disclaimer