With the advancement and widespread adoption of nuclear energy, and the Fukushima nuclear wastewater discharge incident, concerns regarding the environmental risks posed by radioactive elements in aquatic environments are increasing. Cesium-137 ( 137 Cs), a prominent anthropogenic radionuclide, exhibits developmental toxicity in various organisms; however, the precise extent of this environmental risk and the stage-specific molecular mechanisms remain inadequately defined. Here, zebrafish embryos were used to investigate the effects of 137 Cs across various developmental stages, including the proenteral, segmental, hatching, and full cycle stages, and the related mechanisms. Morphological observations at 48 h post-fertilization (hpf) revealed significant ( p < 0.05) embryonic malformations in zebrafish exposed during the hatching stage (S3) and full stage (S4) at 194 and 970 Bq/L, respectively. Concentration-dependent transcriptomic analyses indicated that the biological pathways perturbed by 137 Cs were linked mainly to gene damage repair. These pathways included mRNA 5′-UTR binding, double-strand break repair via break-induced replication, and single-stranded DNA helicase activity, with a point of departure (POD) for effect initiation ≤ 100 Bq/L. Finally, the 137 Cs-enriched biological pathways were integrated into an adverse outcome pathway (AOP) network to quantitatively compare and mechanistically elucidate stage-specific toxicity, revealing four typical AOPs: a reduction in the DHB4/HSD17B4 ratio leading to liver steatosis, induction of adenoma/carcinoma in the proximal tubular epithelium (renal tubules), inhibition of NADH-ubiquinone oxidoreductase leading to neurodegeneration, and tubulin binding resulting in aneuploid offspring. This study introduces a novel methodology for assessing the environmental risks associated with radioactive substances and establishing stage-specific AOP-informed mechanisms critical for refining safety benchmarks. • 137 Cs induces significant malformations in zebrafish embryos at 194 Bq/L. • 137 Cs within 100 Bq/L can induce gene damage repair-related pathways. • Exposure to 137 Cs during gastrula stage can activate neurotoxicity-related pathways. • The AOPs of 137 Cs have been analyzed by concentration-dependent omics. • The 1000 Bq/L radioactive benchmark can not protect aquatic organisms.
Fang et al. (Fri,) studied this question.