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

Abstract : 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [58 references]  Display  Hide  Download

https://www.hal.inserm.fr/inserm-02108873
Contributor : Francois Vallette <>
Submitted on : Wednesday, April 24, 2019 - 2:23:49 PM
Last modification on : Friday, September 13, 2019 - 4:22:06 PM

File

 Restricted access
To satisfy the distribution rights of the publisher, the document is embargoed until : jamais

Please log in to resquest access to the document

Identifiers

Collections

Citation

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, AlphaMed Press, 2017, 35 (3), pp.800-811. ⟨10.1002/stem.2539⟩. ⟨inserm-02108873⟩

Share

Metrics

Record views

79