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

Journal of Hematology & Oncology

Qipan Deng¹  Xiaodong Ma¹  Lei Wang¹  Ming Liu¹  Zhaojian Gong¹  Yong Li¹  Hui Hu¹  Shanshan Zhang¹  Ken H. Young²  Zijun Y. Xu-Monette²  Zhongxin Lu³ 

[1] Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic;Department of Hematopathology, The University of Texas MD Anderson Cancer Center;Department of Medical Laboratory, Central Hospital of Wuhan;

关键词: Glyphosate;    Multiple myeloma;    Vk*MYC mice;    Activation-induced cytidine deaminase;   

DOI  :  10.1186/s13045-019-0767-9

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown