Toxic effects and foundation of proton radiation on the early-life stage of zebrafish development

Proton is a major particle of space radiation environment and a prospective radiotherapy beam. However, its risk needs to be fully evaluated for the understanding and to establish the better protective strategy for astronaut and patient. Zebrafish is an ideal model for the toxicity studies on medicines and environmental genetic toxicants. In the current study, embryos of zebrafish at 24 h post-fertilization (hpf) were exposed to proton beam. Some toxic parameters of embryo-larval development were investigated. Microarray combining with qRT-PCR were used to detect the gene expression situation. Generally, fractions of a variety of abnormal phenotypes of embryos and larvae increased in a dose-dependent manner after irradiation. The copy number of mitochondria, the basal respiration rate and the maximum respiration rate of embryos significantly decreased after irradiation. Microarray data demonstrated that MAPK signaling pathway, cell communication, glycolysis and TGF-β signaling pathway were significantly affected in the irradiated group. The expressions of matrix metallopeptidase 9 (mmp9) and TIMP metallopeptidase inhibitor 2b (timp2b) genes, and enzymatic activity of MMP9 were significantly upregulated in irradiated group. Overall, these results suggest that acute radiation of proton severely affects the development of organism and results in aberration occurrence in the early stage of zebrafish development, which may relates to mitochondrial and glycolytic dysfunction.