| Perfluorinated and polyfluorinated compounds(PFASs)are a class of fluorinated organic compounds with important application value.Due to their environmental persistence,bioaccumulation and biotoxicity,some PFASs have been restricted or banned.Therefore,their substitutes have received more and more attention.1,1,2,2-perfluorooctyl sulfonic acid(6:2 FTS)is a novel substitute for perfluorooctyl sulfonic acid(PFOS)that has been widely existed in a variety of environmental media.The current studies were focused on its environmental behavior,therefor,the toxic effects of 6:2 FTS are needed for further study.In this study,zebrafish and isolated cells,typical aquatic organisms,were selected as toxicity test models,and PFOS was used as positive control to evaluate the biosafety of 6:2 FTS.The main research contents include:(1)zebrafish embryo exposure experiment.We first compared the single acute toxicity of 6:2 FTS and PFOS to zebrafish embryos and calculated the LC50 value.Then according to the LC50 value and microscope observation,low concentration exposure was selected to determine the morphological indexes.On this basis,we focused on cardiovascular toxicity,using gene-edited fish to explore the effects of 6:2 FTS and PFOS on blood vessels and heart development,and the blood flow velocity and behavior were measured simultaneously.Finally,we measured the transcriptome of 96 hpf juvenile fish and validated it at the molecular level.(2)Exposure experiment of adult zebrafish.After 14 days of exposure to low-dose 6:2 FTS and PFOS,pathological tissue sections of the intestine,spleen and heart of the exposed adult zebrafish were performed and analyzed.At the same time,the effects of 6:2 FTS and PFOS on the metabolic small molecules of adult zebrafish were evaluated by metabonomics techniques and did the gene verification.(3)Cytotoxicity experiment.Two types of cancer cells,HepG2 and T24,were selected for exposure experiments.The toxicity effects of 6:2 FTS and PFOS on the two cancer cells were evaluated,LC50 and EC50 values were calculated,and the molecular mechanism of the effects of the two compounds on the migration ability of cancer cells was further studied.The results of embryo exposure showed that 6:2 FTS had lower acute toxicity than PFOS.6:2 FTS could affect the development of zebrafish,including increasing the utilization of yolk sac and the length of pharyngeal pouch,leading to pericardial edema and inhibiting the heart beating.It was found that 6:2 FTS could induce vascular hyperplasia,inhibit atrial development and reduce blood flow velocity in juvenile 72 hpf.At the transcriptional level,the influence of low concentration 6:2 FTS was more significant.2 ?M 6:2 FTS enhanced the activity of CAT and GSH-Px,involved in calcium signal transduction and myocardial contraction,and affected the MAPK,FoxO and p53 signaling pathways.Results of adult fish exposure showed that 0.2 ?M PFOS group had significantly lose weight.Both PFOS and 6:2 FTS caused lesions in the heart,spleen and intestine,and significantly affected the metabolic level.The contents of phosphatidylls,lysophosphatidylls and camitines were significantly decreased after the exposure of PFOS and 6:2 FTS.In PFOS group,deoxycholic acid,taurocholic acid and coenzyme Q were significantly increased and influenced Primary bile acid synthesis,bile secretion and Retrograde endocannnabinoid signaling.The levels of DAG and TAG in 6:2 FTS group were significantly increased,Phosphatidylinositol signaling system,insitol phosphate metabolism and glycerolipid metabolism were influenced.The results of cell exposure showed that the cytotoxicity of 6:2 FTS was lower than that of PFOS.1?M 6:2 FTS could significantly induce the proliferation of HepG2 cells and T24 cells,and could promote cell migration of T24 cells in a short period of time,but 6:2 FTS showed inhibited effects on cell migration with the increase of exposure time.This study systematically evaluated the toxic effects of 6:2 FTS on zebrafish and cells.It was found that the acute toxicity of 6:2 FTS was lower than that of PFOS,however,considering the potential effects on body development,cardiovascular and endocrine disrupting toxicity,aquatic organisms and cytotoxicity of 6:2 FTS should be reassessed to provide scientific data support for chemical management and risk control... |
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