Low-Dose Pesticide Mixture Induces Senescence in Normal Mesenchymal Stem Cells (MSC) and Promotes Tumorigenic Phenotype in Premalignant MSC - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue STEM CELLS Année : 2017

Low-Dose Pesticide Mixture Induces Senescence in Normal Mesenchymal Stem Cells (MSC) and Promotes Tumorigenic Phenotype in Premalignant MSC

Claire Pecqueur

Résumé

Humans are chronically exposed to multiple environmental pollutants such as pesticides with no significant evidence about the safety of such poly-exposures. We exposed mesenchymal stem cells (MSC) to very low doses of mixture of seven pesticides frequently detected in food samples for 21 days in vitro. We observed a permanent phenotype modification with a specific induction of an oxidative stress-related senescence. Pesticide mixture also induced a shift in MSC differentiation towards adipogenesis but did not initiate a tumorigenic transformation. In modified MSC in which a premalignant phenotype was induced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro and in vivo after cell implantation, in all nude mice. Our results suggest that a common combination of pesticides can induce a premature ageing of adult MSC, and as such could accelerate age-related diseases. Exposure to pesticide mixture may also promote the tumorigenic transformation in a predisposed stromal environment. STEM CELLS 2017;35:800-811 SIGNIFICANCE STATEMENT The environmental exposure to pesticides is recognized as a potential threat to human health. However, little is known on the effect of pesticides on stem cells. Here we show that a pesticide mixture, at doses commonly found in western diet, promotes stress-related senescence in normal MSC and tumorigenesis in premalignant MSC. Our results provide a new insight in the effect of pesticides on the acceleration of stem cell ageing and possibly on cancer.
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inserm-02108873 , version 1 (24-04-2019)

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Mazène Hochane, Valérie Trichet, Claire Pecqueur, Pierre Avril, Lisa Oliver, et al.. Low-Dose Pesticide Mixture Induces Senescence in Normal Mesenchymal Stem Cells (MSC) and Promotes Tumorigenic Phenotype in Premalignant MSC. STEM CELLS, 2017, 35 (3), pp.800-811. ⟨10.1002/stem.2539⟩. ⟨inserm-02108873⟩
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