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

J Hematol Oncol. 2019 Jul 5;12(1):70. doi: 10.1186/s13045-019-0767-9.

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.

Keywords: Activation-induced cytidine deaminase; Glyphosate; Multiple myeloma; Vk*MYC mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Progression
  • Female
  • Glycine / adverse effects
  • Glycine / analogs & derivatives*
  • Herbicides / adverse effects*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Monoclonal Gammopathy of Undetermined Significance / blood
  • Monoclonal Gammopathy of Undetermined Significance / chemically induced*
  • Monoclonal Gammopathy of Undetermined Significance / pathology
  • Multiple Myeloma / blood
  • Multiple Myeloma / chemically induced*
  • Multiple Myeloma / pathology
  • Splenomegaly / blood
  • Splenomegaly / chemically induced
  • Splenomegaly / pathology
  • Water Pollutants, Chemical / adverse effects

Substances

  • Herbicides
  • Water Pollutants, Chemical
  • glyphosate
  • Glycine