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Article

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

1
Department of Biological Hematology, Tours University Hospital, 37000 Tours, France
2
CNRS ERL 7001 LNOx, EA 7501, Tours University, 37000 Tours, France
3
INSERM U1241, NuMeCan Institute, 35000 Rennes, France
4
CNRS GDR 3697 Micronit “Microenvironment of Tumor Niches”, 37000 Tours, France
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Cancéropole Grand Ouest (CGO), NET “Niches and Epigenetics of Tumors” Network, 44000 Nantes, France
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Department of Hematology & Cell Therapy, Tours University Hospital, 37000 Tours, France
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Department of Biological Hematology & CRCINA, Nantes University Hospital, 44000 Nantes, France
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Fédération Hospitalo-Universitaire, “Grand Ouest Against Leukemia” (FHU GOAL), 49000 Angers, France
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INSERM UMR 1232 CRCINA, 44000 Nantes, France
10
Faculty of Pharmaceutical and Biological Sciences, Nantes University, 44000 Nantes, France
11
OPALE Carnot Institute, The Organization for Partnerships in Leukemia, Hôpital Saint-Louis, 75010 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editors: Ada Funaro and Nicole M. Gatto
Cancers 2021, 13(22), 5699; https://doi.org/10.3390/cancers13225699
Received: 20 September 2021 / Revised: 29 October 2021 / Accepted: 9 November 2021 / Published: 14 November 2021
(This article belongs to the Special Issue Environmental Carcinogens and Cancer Risk)
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.
(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. View Full-Text
Keywords: hematopoiesis; pesticides; mesenchymal stem/stromal cells; ALDH2; myelodysplastic syndrome hematopoiesis; pesticides; mesenchymal stem/stromal cells; ALDH2; myelodysplastic syndrome
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MDPI and ACS Style

Foucault, A.; Ravalet, N.; Besombes, J.; Picou, F.; Gallay, N.; Babin, L.; Bourgeais, J.; Hamard, S.; Domenech, J.; Loyer, P.; Vallet, N.; Lejeune, J.; Gyan, E.; Béné, M.C.; Vallette, F.; Olivier, C.; Hérault, O. Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition. Cancers 2021, 13, 5699. https://doi.org/10.3390/cancers13225699

AMA Style

Foucault A, Ravalet N, Besombes J, Picou F, Gallay N, Babin L, Bourgeais J, Hamard S, Domenech J, Loyer P, Vallet N, Lejeune J, Gyan E, Béné MC, Vallette F, Olivier C, Hérault O. Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition. Cancers. 2021; 13(22):5699. https://doi.org/10.3390/cancers13225699

Chicago/Turabian Style

Foucault, Amélie, 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, and Olivier Hérault. 2021. "Low-Dose Pesticides Alter Primary Human Bone Marrow Mesenchymal Stem/Stromal Cells through ALDH2 Inhibition" Cancers 13, no. 22: 5699. https://doi.org/10.3390/cancers13225699

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