2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice

Lei Wang, Munish Kumar, Qipan Deng, Xu Wang, Ming Liu, Zhaojian Gong, Shanshan Zhang, Xiaodong Ma, Zijun Y. Xu-Monette, Min Xiao, Qing Yi, Ken H. Young, Kenneth Ramos, Yong Li

Research output: Contribution to journalArticle

Abstract

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 tubular casts, 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.

LanguageEnglish (US)
Pages135-144
Number of pages10
JournalCancer Letters
Volume440-441
DOIs
StatePublished - Jan 1 2019

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Plasma Cell Neoplasms
Multiple Myeloma
Blood Cells
Monoclonal Gammopathy of Undetermined Significance
Anemia
Spleen
Immunoglobulin G
Bone Marrow
Paraproteinemias
Polychlorinated Dibenzodioxins
Splenomegaly
Kidney Diseases
Occupational Exposure
Plasma Cells
Serum
Inbred C57BL Mouse
DNA Damage
Epidemiologic Studies
Kidney
Bone and Bones

Keywords

  • Mice
  • Multiple myeloma
  • TCDD
  • Vk*Myc

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice. / Wang, Lei; Kumar, Munish; Deng, Qipan; Wang, Xu; Liu, Ming; Gong, Zhaojian; Zhang, Shanshan; Ma, Xiaodong; Xu-Monette, Zijun Y.; Xiao, Min; Yi, Qing; Young, Ken H.; Ramos, Kenneth; Li, Yong.

In: Cancer Letters, Vol. 440-441, 01.01.2019, p. 135-144.

Research output: Contribution to journalArticle

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, K & Li, Y 2019, '2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice' Cancer Letters, vol. 440-441, pp. 135-144. https://doi.org/10.1016/j.canlet.2018.10.009
Wang, Lei ; Kumar, Munish ; Deng, Qipan ; Wang, Xu ; Liu, Ming ; Gong, Zhaojian ; Zhang, Shanshan ; Ma, Xiaodong ; Xu-Monette, Zijun Y. ; Xiao, Min ; Yi, Qing ; Young, Ken H. ; Ramos, Kenneth ; Li, Yong. / 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces peripheral blood abnormalities and plasma cell neoplasms resembling multiple myeloma in mice. In: Cancer Letters. 2019 ; Vol. 440-441. pp. 135-144.
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abstract = "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 tubular casts, 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.",
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AU - Deng, Qipan

AU - Wang, Xu

AU - Liu, Ming

AU - Gong, Zhaojian

AU - Zhang, Shanshan

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AU - Young, Ken H.

AU - Ramos, Kenneth

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