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

SIMPLE SUMMARY: Pesticide exposure is a public health concern. Two recent studies reported that exposure of normal primary bone marrow mesenchymal stem/stromal cells (BM-MSCs) to low-dose pesticide mixture induces deleterious consequences, such as oxidative stress, senescence, accelerated aging and...

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Autores principales: Foucault, Amélie, Ravalet, Noémie, 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616329/
https://www.ncbi.nlm.nih.gov/pubmed/34830855
http://dx.doi.org/10.3390/cancers13225699
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author Foucault, Amélie
Ravalet, Noémie
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
author_facet Foucault, Amélie
Ravalet, Noémie
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
author_sort Foucault, Amélie
collection PubMed
description SIMPLE SUMMARY: Pesticide exposure is a public health concern. Two recent studies reported that exposure of normal primary bone marrow mesenchymal stem/stromal cells (BM-MSCs) to low-dose pesticide mixture induces deleterious consequences, such as oxidative stress, senescence, accelerated aging and increased sensitivity to oncogenic hits. Here, we show that exposure to this mixture decreases aldehyde dehydrogenase-2 (ALDH2) activity, with a concomitant increase in acetaldehyde level and DNA damage and alters the MSC capacity to support primitive hematopoiesis. Similar abnormalities were observed in bone marrow-MSCs from patients suffering from myelodysplastic syndrome (MDS), suggesting a role of pesticide-induced ALDH2 inhibition in the pathophysiology of this pre-leukemic disease. ABSTRACT: (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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spelling pubmed-86163292021-11-26 Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition Foucault, Amélie Ravalet, Noémie 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 Cancers (Basel) Article SIMPLE SUMMARY: Pesticide exposure is a public health concern. Two recent studies reported that exposure of normal primary bone marrow mesenchymal stem/stromal cells (BM-MSCs) to low-dose pesticide mixture induces deleterious consequences, such as oxidative stress, senescence, accelerated aging and increased sensitivity to oncogenic hits. Here, we show that exposure to this mixture decreases aldehyde dehydrogenase-2 (ALDH2) activity, with a concomitant increase in acetaldehyde level and DNA damage and alters the MSC capacity to support primitive hematopoiesis. Similar abnormalities were observed in bone marrow-MSCs from patients suffering from myelodysplastic syndrome (MDS), suggesting a role of pesticide-induced ALDH2 inhibition in the pathophysiology of this pre-leukemic disease. ABSTRACT: (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. MDPI 2021-11-14 /pmc/articles/PMC8616329/ /pubmed/34830855 http://dx.doi.org/10.3390/cancers13225699 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Foucault, Amélie
Ravalet, Noémie
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
Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616329/
https://www.ncbi.nlm.nih.gov/pubmed/34830855
http://dx.doi.org/10.3390/cancers13225699
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