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Stem Cells. 2017 Mar;35(3):800-811. doi: 10.1002/stem.2539. Epub 2016 Nov 23.

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

Hochane M1,2, Trichet V2,3,4, Pecqueur C1,2, Avril P2,3,4, Oliver L1,2,5, Denis J1,2, Brion R2,3,4,5, Amiaud J2,3,4, Pineau A6,7, Naveilhan P2,8, Heymann D2,3,4,5, Vallette FM1,2,9, Olivier C1,7.

Author information

1
Centre de Recherche en Cancérologie Nantes Angers UMR INSERM 892, CNRS 6299 - Equipe 9, Université de Nantes, Nantes, France.
2
Faculté de Médecine, Université de Nantes, Nantes, France.
3
INSERM, UMR 957, Equipe Ligue 2012, Nantes, France.
4
Faculty of Medicine, Pathophysiology of Bone Resorption Laboratory and Therapy of Primary Bone Tumours University of Nantes, Nantes, France.
5
CHU de Nantes, Nantes, France.
6
Department of Pharmacology and Toxicology, University Hospital of Nantes, Nantes, France.
7
Service de toxicologie, Faculté de pharmacie de Nantes.
8
INSERM UMR 913, IMAD, France.
9
LaBCT, Institut de Cancérologie de l'Ouest, Nantes, France.

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. Abstract Video Link: https://youtu.be/mfSVPTol-Gk Stem Cells 2017;35:800-811.

KEYWORDS:

mesenchymal stem cells; pesticide mixture; pesticides; senescence; tumorigenesis

PMID:
27860054
DOI:
10.1002/stem.2539
[Indexed for MEDLINE]
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