Electron dose rate and oxygen depletion protect zebrafish embryos from radiation damage

Abstract

Background and purpose: In consequence of a previous study, where no protecting proton Flash effect was found for zebrafish embryos, potential reasons and requirements for inducing a Flash effect should be investigated with higher pulse dose rate and partial oxygen pressure (pO₂) as relevant parameters.

Materials and methods: The experiments were performed at the research electron accelerator ELBE, whose variable pulse structure enables dose delivery as electron Flash and quasi-continuously (reference irradiation). Zebrafish embryos were irradiated with ~26 Gy either continuously at a dose rate of ~6.7 Gy/min (reference) or by 1441 electron pulses within 111 µs at a pulse dose rate of 10⁹ Gy/s and a mean dose rate of 10⁵Gy/s, respectively. Using the OxyLite system to measure the pO₂ a low- (pO₂ ≤ 5 mmHg) and a high-pO₂ group were defined on basis of the oxygen depletion kinetics in sealed embryo samples.

Results: A protective Flash effect was seen for most endpoints ranging from 4 % less reduction in embryo length to about 20-25% less embryos with spinal curvature and pericardial edema, relative to reference irradiation. The reduction of pO₂ below atmospheric levels (148 mmHg) resulted in higher protection, which was however more pronounced in the low-pO₂ group.

Conclusion: The Flash experiment at ELBE showed that the zebrafish embryo model is appropriate for studying the radiobiological response of high dose rate irradiation. The applied high pulse dose rate was confirmed as important beam parameter as well as the pivotal role of pO₂ during irradiation.

Keywords: Electron flash effect; Normal tissue toxicity; Oxygen depletion; Zebrafish embryo.