Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
School of Life Sciences, Institute of Modern Aquaculture Science and Engineering, Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, South China Normal University, Guangzhou, 510631, China.
J Hematol Oncol. 2019 Jul 5;12(1):70. doi: 10.1186/s13045-019-0767-9.
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.
VkMYC is a mouse line with sporadic MYC activation in germinal center B cells and considered as the best available MM animal model. We treated VkMYC mice and wild-type mice with drinking water containing 1000 mg/L of glyphosate and examined animals after 72 weeks.
VkMYC 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 VkMYC 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.
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.
草甘膦是美国乃至全球使用最广泛的除草剂。关于其致癌性存在相当大的争议。流行病学研究表明，多发性骨髓瘤（MM）和非霍奇金淋巴瘤（NHL）与草甘膦暴露呈正相关且具有统计学意义。作为 B 细胞基因组诱变剂，激活诱导胞苷脱氨酶（AID）是 MM 和 B 细胞 NHL 的关键致病因素。
VkMYC 是一种在生发中心 B 细胞中具有散发性 MYC 激活的小鼠品系，被认为是最先进的 MM 动物模型。我们用含有 1000mg/L 草甘膦的饮用水处理 VkMYC 小鼠和野生型小鼠，并在 72 周后检查动物。
暴露于草甘膦的 VkMYC 小鼠出现进行性血液学异常和浆细胞瘤，如脾肿大、贫血和高血清 IgG。此外，草甘膦导致 VkMYC 小鼠多器官功能障碍，包括溶骨性骨病变和肾脏损伤。用草甘膦处理的野生型小鼠出现良性单克隆丙种球蛋白病，伴有血清 IgG 增加、贫血和脾和骨髓中浆细胞存在。最后，草甘膦上调了野生型和 Vk*MYC 小鼠脾和骨髓中的 AID。
这些数据支持草甘膦是 MM 以及潜在 NHL 的环境风险因素，并提示了流行病学观察到的草甘膦诱导致癌作用中 B 细胞特异性的潜在机制。
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