Impacts of PFOAC8, GenXC6, and their mixtures on zebrafish developmental toxicity and gene expression provide insight about tumor-related disease

Concerns about per- and polyfluoroalkyl substances (PFASs) have grown in importance in the fields of ecotoxicology and public health. This study aims to compare the potential effects of long-chain (carbon atoms ≥ 7) and short-chain derivatives and their mixtures' exposure according to PFASs-exposed (1, 2, 5, 10, and 20 mg/L) zebrafish's (Danio rerio) toxic effects and their differential gene expression. Here, PFOAC8, GenXC6, and their mixtures (v/v, 1:1) could reduce embryo hatchability and increase teratogenicity and mortality. The toxicity of PFOAC8 was higher than that of GenXC6, and the toxicity of their mixtures was irregular. Their exposure (2 mg/L) caused zebrafish ventricular edema, malformation of the spine, blood accumulation, or developmental delay. In addition, all of them had significant differences in gene expression. PFOAC8 exposure causes overall genetic changes, and the pathways of this transformation were autophagy and apoptosis. More importantly, in order to protect cells from PFOAC8, GenXC6, and their mixtures' influences, zebrafish inhibited the expression of ATPase and Ca2+ transport gene (atp1b2b), mitochondrial function-related regulatory genes (mt-co2, mt-co3, and mt-cyb), and tumor or carcinogenic cell proliferation genes (laptm4b and ctsbb). Overall, PFOAC8, GenXC6, and their mixtures' exposures will affect the gene expression effects of zebrafish embryos, indicating that PFASs may pose a potential threat to aquatic biological safety. These results showed that the relevant genes in zebrafish that were inhibited by PFASs exposure were related to tumorigenesis. Therefore, the effect of PFASs on zebrafish can be further used to study the pathogenesis of tumors. [Display omitted] •PFOA is more toxic than GenX to apoptosis and autophagy.•PFOA+GenX exposure has additive and synergistic effects.•PFASs significantly inhibited tumor-related disease gene expression.•PFASs play a dual role in organ and tissue teratogenic processes.