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

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

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.

MeSH terms

  • Adipogenesis / drug effects
  • Animals
  • Carcinogenesis / drug effects
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology*
  • Cell Differentiation / drug effects
  • Cell Respiration
  • Cellular Senescence
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Female
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mesenchymal Stem Cells / pathology*
  • Mice, Nude
  • Pesticides / toxicity*
  • Phenotype
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Reactive Oxygen Species / metabolism
  • Stress, Physiological
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Pesticides
  • Reactive Oxygen Species
  • Tumor Suppressor Protein p53