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Toxicology ; 505: 153844, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38801937

RESUMO

Tributyltin chloride (TBTC) is a ubiquitous environmental pollutant with various adverse effects on human health. Exosomes are cell - derived signaling and substance transport vesicles. This investigation aimed to explore whether exosomes could impact the toxic effects caused by TBTC via their transport function. Cytotoxicity, DNA and chromosome damage caused by TBTC on MCF-7 cells were analyzed with CCK-8, flow cytometry, comet assay and micronucleus tests, respectively. Exosomal characterization and quantitative analysis were performed with ultracentrifugation, transmission electron microscope (TEM) and bicinchoninic acid (BCA) methods. TBTC content in exosomes was detected with Liquid Chromatography-Mass Spectrometry (LC-MS). The impacts of exosomal secretion on the toxic effects of TBTC were analyzed. Our data indicated that TBTC caused significant cytotoxicity, DNA and chromosome damage effects on MCF-7 cells, and a significantly increased exosomal secretion. Importantly, TBTC could be transported out of MCF-7 cells by exosomes. Further, when exosomal secretion was blocked with GW4869, the toxic effects of TBTC were significantly exacerbated. We concluded that TBTC promoted exosomal secretion, which in turn transported TBTC out of the source cells to alleviate its toxic effects. This investigation provided a novel insight into the role and mechanism of exosomal release under TBTC stress.


Assuntos
Dano ao DNA , Exossomos , Compostos de Trialquitina , Humanos , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Compostos de Trialquitina/toxicidade , Células MCF-7 , Dano ao DNA/efeitos dos fármacos , Transporte Biológico/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Sobrevivência Celular/efeitos dos fármacos
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