Impact of Low-level Ionizing Radiation on Cell Death During Zebrafish Embryonic Development

Abstract

Ionizing radiation (IR) has been linked to multiple types of cellular responses, but its effects on developing organisms are still poorly understood. The authors investigated whether zebrafish embryos exhibit differential responses relative to IR dose and developmental age at time of exposure. Early-stage zebrafish embryos were exposed to different levels of gamma radiation and then, at varying points after irradiation, assayed for morphological defects and levels of cell death. To quantify in vivo cellular responses to low-dose IR exposure and explore how tissue-specific cell functions affect radiation response, apoptotic cells were counted in three regions: the tail, urogenital papilla, and left eye. The authors found that increased gamma radiation doses correlated with increased levels of apoptosis in the developing tail and eye, whereas cells of the urogenital papilla appeared to undergo apoptosis independently of radiation dose. This suggests that the linear-no-threshold model may not be appropriate in all contexts. Grouping embryos by age at IR exposure revealed that gamma radiation exposure resulted in higher levels of apoptosis in embryos irradiated at 2 d post fertilization (dpf), suggesting a radiosensitive stage of development. Moreover, levels of apoptosis were statistically influenced by days grown after irradiation, with embryos fixed at later stages showing more dramatic apoptotic responses to radiation exposure. This latency to effect suggests potential competition between DNA repair and apoptosis pathways, which may lead to the accumulation of apoptotic cells only after an initial lag period.

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model

“…Furthermore, our measurements detected a notable reduction in body length, which suggests spinal cord curvature and growth delay. It is well known that different radiation qualities cause developmental deteriorations (41)(42)(43)(44), but only a few studies measured the degree of spinal curvature (19,20) and confirmed a linear dose dependent increase in severity on the fourth dpi at a dose level of 10 Gy or higher. Sayed and Mitani (45) showed spinal cord abnormality (body curvature) in the embryos of fish (Medaka) even after exposure to UV-A irradiation.…”

High Doses of Radiation Cause Cochlear Immunological Stress and Sensorineural Hearing Loss

“…The causes of bystander cell damage are as follows: On the one hand, ionizing radiation can directly cause DNA damage and cell death. On the other hand, radiation can indirectly promote cellcycle arrest, cell senescence, necrosis, or apoptosis through excessive oxidative stress and inflammation [12,32], which eventually leads to tissue microenvironment destruction and functional disorder [33]. During the treatment of head and neck cancer, sensorineural hearing loss is one of the "radiation-induced bystander effects".…”

“…It is also reported that the cochlear ribbon synapse is very sensitive to ionizing radiation, and this pathological change can occur in the acute phase after irradiation [11]. Radiation-induced tissue cell death is confirmed with the generation of ROS and the consequent activation of caspase, inflammation, apoptosis [12], and/or necrosis [13]. The biological functions of the body's immune system are diverse.…”