2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice.
复制标题
2,3,7,8-四氯二苯并-对二恶英 (TCDD) 诱导小鼠外周血异常和浆细胞肿瘤，类似于多发性骨髓瘤
DOI：
10.1016/j.canlet.2018.10.009
复制
发表时间：
2019-01
期刊：
影响因子：
9.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang L;Kumar M;Deng Q;Wang X;Liu M;Gong Z;Zhang S;Ma X;Xu-Monette ZY;Xiao M;Yi Q;Young KH;Ramos KS;Li Y
虽然流行病学研究表明，职业暴露于2，3，7，8-四氯二苯并对二恶英（TCDD）和多发性骨髓瘤的发展风险之间可能存在关联，但缺乏支持这种关联的明确证据。在本研究中，我们采用了多发性骨髓瘤的Vk*Myc小鼠模型，以评估TCDD暴露对多发性骨髓瘤发病机制的影响。TCDD引起脾肿大和多种外周血异常，包括贫血和高血清IgG水平。此外，TCDD引发骨溶解性病变以及肾蛋白沉积，这是与人类骨髓瘤肾病相关的现象。即使在野生型C57 BL/6小鼠中，TCDD也会增加血清IgG水平，诱发贫血，并增加脾脏和骨髓中的浆细胞，这是良性单克隆丙种球蛋白病的标志。最后，TCDD诱导AKT激活和DNA损伤反应，骨髓瘤发病机制中的关键致病事件，在动物脾脏和/或骨髓。这些数据表明，TCDD加速单克隆丙种球蛋白病的发展，并促进遗传易感小鼠向多发性骨髓瘤的进展。这项工作提供了第一个直接的实验证据，建立TCDD作为一个环境的危险因素，单克隆丙种球蛋白病的意义不明和多发性骨髓瘤。
Although epidemiologic studies have suggested a possible association between occupational exposures to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the risk of development of multiple myeloma, definitive evidence in support of this association is lacking. In the present study, we employed the Vk*Myc mouse model of multiple myeloma to assess the impact of TCDD exposure on multiple myeloma pathogenesis. TCDD induced splenomegaly and multiple peripheral blood abnormalities, including anemia and high serum IgG levels. In addition, TCDD triggered bone lytic lesions, as well as renal protein deposition, a phenomenon associated with human myeloma kidney disease. Even in wild-type C57BL/6 mice, TCDD increased serum IgG levels, induced anemia, and increased plasma cell presence in the spleen and bone marrow, hallmarks of benign monoclonal gammopathy. Lastly, TCDD induced AKT activation and the DNA damage response, key pathogenic events in myeloma pathogenesis, in animal spleen and/or bone marrow. These data indicate that TCDD accelerates monoclonal gammopathy development and promotes progression to multiple myeloma in genetically-predisposed mice. This work offers the first direct experimental evidence establishing TCDD as an environmental risk factor for monoclonal gammopathy of undetermined significance and multiple myeloma.
登录
查看更多内容
影响因子：
11.4
作者：
Chng, W-J;Huang, G. F.;Chung, T. H.;Ng, S. B.;Gonzalez-Paz, N.;Troska-Price, T.;Mulligan, G.;Chesi, M.;Bergsagel, P. L.;Fonseca, R.
通讯作者：
Fonseca, R.
影响因子：
28.2
作者：
Cottini F;Hideshima T;Suzuki R;Tai YT;Bianchini G;Richardson PG;Anderson KC;Tonon G
通讯作者：
Tonon G
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
2,3,7,8-四氯二苯并-对二恶英 (TCDD) 通过激活 Akt 和 NF-kappa B 信号通路诱导 C57BL6 小鼠肝星状细胞 (HSC) 活化和肝纤维化
影响因子：
3.5
作者：
Han, Ming;Liu, Xipeng;Xu, Guangfei
通讯作者：
Xu, Guangfei
影响因子：
12.8
作者：
Castillo, Jorge J.;Dhami, Pradeep K.;Brennan, Keith
通讯作者：
Brennan, Keith