Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
2021
Foucault, Amélie | Ravalet, Noemie | Besombes, Joevin | Picou, Frédéric | Gallay, Nathalie | Babin, Laetitia | Bourgeais, Jérôme | Hamard, Sophie | Domenech, Jorge | Loyer, Pascal | Vallet, Nicolas | Lejeune, Julien | Gyan, Emmanuel | Béné, Marie C | Vallette, François | Olivier, Christophe | Hérault, Olivier | Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-.2022] (GICC EA 7501) ; Université de Tours (UT) | ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx) ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-.2022] (GICC EA 7501) ; Université de Tours (UT)-Université de Tours (UT) | Nutrition, Métabolismes et Cancer (NuMeCan) ; Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Cancéropôle Grand-Ouest [Bretagne-Centre-Pays de Loire] | CHU Trousseau [Tours] ; Centre Hospitalier Régional Universitaire de Tours (CHRU Tours) | Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes) | Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA) ; Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Universitaire de Nantes = Nantes University Hospital (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE) ; Université de Nantes (UN)-Université de Nantes (UN) | This research was supported by grants from French Cancéropôle Grand-Ouest (AOS 2016/PENICA project).
International audience
Show more [+] Less [-]English. (1) Background: The impact of occupational exposure to high doses of pesticides on hematologic disorders is widely studied. Yet, lifelong exposure to low doses of pesticides, and more particularly their cocktail effect, although poorly known, could also participate to the development of such hematological diseases as myelodysplastic syndrome (MDS) in elderly patients. (2) Methods: In this study, a cocktail of seven pesticides frequently present in water and food (maneb, mancozeb, iprodione, imazalil, chlorpyrifos ethyl, diazinon and dimethoate), as determined by the European Food Safety Authority, were selected. Their in vitro effects at low-doses on primary BM-MSCs from healthy volunteers were examined. (3) Results: Exposure of normal BM-MSCs to pesticides for 21 days inhibited cell proliferation and promoted DNA damage and senescence. Concomitantly, these cells presented a decrease in aldehyde dehydrogenase 2 (ALDH2: mRNA, protein and enzymatic activity) and an increase in acetaldehyde levels. Pharmacological inhibition of ALDH2 with disulfiram recapitulated the alterations induced by exposure to low doses of pesticides. Moreover, BM-MSCs capacity to support primitive hematopoiesis was significantly altered. Similar biological abnormalities were found in primary BM-MSCs derived from MDS patients. (4) Conclusions: these results suggest that ALDH2 could participate in the pathophysiology of MDS in elderly people long exposed to low doses of pesticides.
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