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Acceleration of Autoimmunity by Organochlorine Pesticides in (Nzb Versus Nzw)F1 Mice

By Sobel, Eric S.

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Book Id: WPLBN0000226110
Format Type: PDF eBook
File Size: 1.5 MB
Reproduction Date: 2005
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Title: Acceleration of Autoimmunity by Organochlorine Pesticides in (Nzb Versus Nzw)F1 Mice  
Author: Sobel, Eric S.
Language: English
Subject: Government publications, United Nations., United Nations. Office for Disarmament Affairs
Collections: Government Library Collection, Disarmament Documents
Publication Date:
Publisher: United Nations- Office for Disarmament Affairs (Unoda)


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Sobel, E. S. (n.d.). Acceleration of Autoimmunity by Organochlorine Pesticides in (Nzb Versus Nzw)F1 Mice. Retrieved from

Government Reference Publication

Excerpt: Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects women more frequently than men. In the (NZB ? NZW)F1 mouse, a murine SLE model, the presence or absence of estrogen markedly influences the rate of progression of disease. Three organochlorine pesticides with estrogenic effects were administered chronically to ovariectomized female (NZB ? NZW)F1 mice, and we measured the time to development of renal disease, the principal clinical manifestation of lupus in this model. Treatment with chlordecone, methoxychlor, or o,p-dichlorodiphenyltrichloroethane (o,p-DDT) significantly decreased the time to onset of renal impairment, as did treatment with 17(Beta)-estradiol used as a positive control. In an expanded study of chlordecone, we found a dose-related early appearance of elevated anti?double-strand DNA autoantibody titers that corresponded with subsequent development of glomerulonephritis. Immunohistofluorescence confirmed early deposition of immune complexes in kidneys of mice treated with chlordecone. These observations are consistent with an effect of these organochlorine pesticides to accelerate the natural course of SLE in the (NZB ? NZW)F1 mouse. Although we originally hypothesized that the effect on progression of autoimmunity was due to estrogenic properties of the pesticides, autoimmune effects and estrogenicity, assessed through measurement of uterine hypertrophy, were not well correlated. This may indicate that uterine hypertrophy is a poor indicator of comparative estrogenic effects of organochlorine pesticides on the immune system, or that the pesticides are influencing autoimmunity through a mode of action unrelated to their estrogenicity. Key words: autoimmunity, chlordecone, DDT, estrogenicity, glomerulonephritis, kepone, methoxychlor, organochlorine pesticides, systemic lupus erythematosus. Environ Health Perspect 113:323?328 (2005). doi:10.1289/ehp.7347 [2 December 2004].


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