Heymann, D. orcid.org/0000-0001-7777-0669, Hochant, M., Pecqueur, C. et al. (9 more authors) (2016) Low-dose pesticide mixture induces senescence in normal mesenchymal stem cells (MSC) and promotes tumorigenic phenotype in premalignant MSC. Stem Cell. ISSN 1066-5099
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 wasinduced, the exposure to pesticide mixture promoted tumorigenic phenotype both in vitro andin vivo after cell implantation, in all nude mice. Our results suggest that a commoncombination of pesticides can induce a premature ageing of adult MSC, and as such couldaccelerate age-related diseases. Exposure to pesticide mixture may also promote thetumorigenic transformation in a predisposed stromal environment.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 AlphaMed Press. This is an author produced version of a paper subsequently published in STEM CELLS . Uploaded in accordance with the publisher's self-archiving policy |
Keywords: | mesenchymal stem cells; pesticides; pesticide mixture; senes-cence; tumorigenesis |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 16 Nov 2016 13:46 |
Last Modified: | 30 Jun 2017 22:23 |
Published Version: | https://doi.org/10.1002/stem.2539 |
Status: | Published |
Publisher: | AlphaMed Press |
Refereed: | Yes |
Identification Number: | 10.1002/stem.2539 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:106587 |