Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition

(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 hematol...

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Autores principales:	Amélie Foucault, Noémie Ravalet, Joevin Besombes, Frédéric Picou, Nathalie Gallay, Laetitia Babin, Jérôme Bourgeais, Sophie Hamard, Jorge Domenech, Pascal Loyer, Nicolas Vallet, Julien Lejeune, Emmanuel Gyan, Marie C. Béné, François Vallette, Christophe Olivier, Olivier Hérault
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	hematopoiesis pesticides mesenchymal stem/stromal cells ALDH2 myelodysplastic syndrome Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/785966ac32a243c698d778404d6f8960
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spelling	oai:doaj.org-article:785966ac32a243c698d778404d6f89602021-11-25T17:02:49ZLow-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition10.3390/cancers132256992072-6694https://doaj.org/article/785966ac32a243c698d778404d6f89602021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5699https://doaj.org/toc/2072-6694(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.Amélie FoucaultNoémie RavaletJoevin BesombesFrédéric PicouNathalie GallayLaetitia BabinJérôme BourgeaisSophie HamardJorge DomenechPascal LoyerNicolas ValletJulien LejeuneEmmanuel GyanMarie C. BénéFrançois ValletteChristophe OlivierOlivier HéraultMDPI AGarticlehematopoiesispesticidesmesenchymal stem/stromal cellsALDH2myelodysplastic syndromeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5699, p 5699 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hematopoiesis pesticides mesenchymal stem/stromal cells ALDH2 myelodysplastic syndrome Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	hematopoiesis pesticides mesenchymal stem/stromal cells ALDH2 myelodysplastic syndrome Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Amélie Foucault Noémie Ravalet Joevin Besombes Frédéric Picou Nathalie Gallay Laetitia Babin Jérôme Bourgeais Sophie Hamard Jorge Domenech Pascal Loyer Nicolas Vallet Julien Lejeune Emmanuel Gyan Marie C. Béné François Vallette Christophe Olivier Olivier Hérault Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
description	(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.
format	article
author	Amélie Foucault Noémie Ravalet Joevin Besombes Frédéric Picou Nathalie Gallay Laetitia Babin Jérôme Bourgeais Sophie Hamard Jorge Domenech Pascal Loyer Nicolas Vallet Julien Lejeune Emmanuel Gyan Marie C. Béné François Vallette Christophe Olivier Olivier Hérault
author_facet	Amélie Foucault Noémie Ravalet Joevin Besombes Frédéric Picou Nathalie Gallay Laetitia Babin Jérôme Bourgeais Sophie Hamard Jorge Domenech Pascal Loyer Nicolas Vallet Julien Lejeune Emmanuel Gyan Marie C. Béné François Vallette Christophe Olivier Olivier Hérault
author_sort	Amélie Foucault
title	Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title_short	Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title_full	Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title_fullStr	Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title_full_unstemmed	Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title_sort	low-dose pesticides alter primary human bone marrow mesenchymal stem/stromal cells through aldh2 inhibition
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/785966ac32a243c698d778404d6f8960
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Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition

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