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

  • Wang, Lei1, 2
  • Deng, Qipan1
  • Hu, Hui1, 3
  • Liu, Ming1, 4
  • Gong, Zhaojian1, 5
  • Zhang, Shanshan1, 6
  • Xu-Monette, Zijun Y.7
  • Lu, Zhongxin3
  • Young, Ken H.7
  • Ma, Xiaodong1, 8, 9
  • Li, Yong1
  • 1 Lerner Research Institute, Cleveland Clinic, Department of Cancer Biology, Cleveland, OH, USA , Cleveland (United States)
  • 2 South China Normal University, School of Life Sciences, Institute of Modern Aquaculture Science and Engineering, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, Guangzhou, 510631, China , Guangzhou (China)
  • 3 Central Hospital of Wuhan, Department of Medical Laboratory, Wuhan, China , Wuhan (China)
  • 4 Guangzhou Medical University, State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China , Guangzhou (China)
  • 5 Central South University, Department of Stomatology, the Second Xiangya Hospital, Changsha, China , Changsha (China)
  • 6 Central South University, Department of Stomatology, Xiangya Hospital, Changsha, China , Changsha (China)
  • 7 The University of Texas MD Anderson Cancer Center, Department of Hematopathology, Houston, TX, USA , Houston (United States)
  • 8 South China Normal University, Institute for Brain Research and Rehabilitation, Guangzhou, 510631, China , Guangzhou (China)
  • 9 Guangzhou University of Chinese Medicine, The Research Center of Basic Integrative Medicine, Guangzhou, 510006, China , Guangzhou (China)
Published Article
Journal of Hematology & Oncology
Springer Science and Business Media LLC
Publication Date
Jul 05, 2019
DOI: 10.1186/s13045-019-0767-9
Springer Nature


BackgroundGlyphosate 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.MethodsVk*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.ResultsVk*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.ConclusionsThese 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.

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