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Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice

BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with gl...

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Autores principales: Wang, Lei, Deng, Qipan, Hu, Hui, Liu, Ming, Gong, Zhaojian, Zhang, Shanshan, Xu-Monette, Zijun Y., Lu, Zhongxin, Young, Ken H., Ma, Xiaodong, Li, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612199/
https://www.ncbi.nlm.nih.gov/pubmed/31277689
http://dx.doi.org/10.1186/s13045-019-0767-9
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author Wang, Lei
Deng, Qipan
Hu, Hui
Liu, Ming
Gong, Zhaojian
Zhang, Shanshan
Xu-Monette, Zijun Y.
Lu, Zhongxin
Young, Ken H.
Ma, Xiaodong
Li, Yong
author_facet Wang, Lei
Deng, Qipan
Hu, Hui
Liu, Ming
Gong, Zhaojian
Zhang, Shanshan
Xu-Monette, Zijun Y.
Lu, Zhongxin
Young, Ken H.
Ma, Xiaodong
Li, Yong
author_sort Wang, Lei
collection PubMed
description BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL. METHODS: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks. RESULTS: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice. CONCLUSIONS: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-019-0767-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-66121992019-07-16 Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice Wang, Lei Deng, Qipan Hu, Hui Liu, Ming Gong, Zhaojian Zhang, Shanshan Xu-Monette, Zijun Y. Lu, Zhongxin Young, Ken H. Ma, Xiaodong Li, Yong J Hematol Oncol Research BACKGROUND: Glyphosate is the most widely used herbicide in the USA and worldwide. There has been considerable debate about its carcinogenicity. Epidemiological studies suggest that multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) have a positive and statistically significant association with glyphosate exposure. As a B cell genome mutator, activation-induced cytidine deaminase (AID) is a key pathogenic player in both MM and B cell NHL. METHODS: Vk*MYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated Vk*MYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks. RESULTS: Vk*MYC mice under glyphosate exposure developed progressive hematological abnormalities and plasma cell neoplasms such as splenomegaly, anemia, and high serum IgG. Moreover, glyphosate caused multiple organ dysfunction, including lytic bone lesions and renal damage in Vk*MYC mice. Glyphosate-treated wild-type mice developed benign monoclonal gammopathy with increased serum IgG, anemia, and plasma cell presence in the spleen and bone marrow. Finally, glyphosate upregulated AID in the spleen and bone marrow of both wild-type and Vk*MYC mice. CONCLUSIONS: These data support glyphosate as an environmental risk factor for MM and potentially NHL and implicate a mechanism underlying the B cell-specificity of glyphosate-induced carcinogenesis observed epidemiologically. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13045-019-0767-9) contains supplementary material, which is available to authorized users. BioMed Central 2019-07-05 /pmc/articles/PMC6612199/ /pubmed/31277689 http://dx.doi.org/10.1186/s13045-019-0767-9 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wang, Lei
Deng, Qipan
Hu, Hui
Liu, Ming
Gong, Zhaojian
Zhang, Shanshan
Xu-Monette, Zijun Y.
Lu, Zhongxin
Young, Ken H.
Ma, Xiaodong
Li, Yong
Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title_full Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title_fullStr Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title_full_unstemmed Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title_short Glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
title_sort glyphosate induces benign monoclonal gammopathy and promotes multiple myeloma progression in mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6612199/
https://www.ncbi.nlm.nih.gov/pubmed/31277689
http://dx.doi.org/10.1186/s13045-019-0767-9
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