الفهرس 
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Abstract
Autoimmunity induced by chemicals is a recently rt cognized environmental hazard that may affect individuals genetically predh posed to autoimmune diseases and chronically exposed to certain chemicals or drugs. Systemic autoimmune diseases can be induced experimentally in J odents by chemicals such as HgC12 and DP. These models share several featw s such as production of antinuclear antibodies, immune glomerulonephril is , MHC class II hyperexpression on B cells, hyper IgE , increased IL-4 ac ivity and impairment of IL-2 production.
Treatment of A.SW mice with HgCl2 produced high titer of ANucA , started at 2 weeks from treatment, peaked at 6 weeks and then remained constant until the end of treatment. These ANucA reacted with 34 - 36 kD ( fibrillarin) and 64 - 74 kD nucleolar proteins in immunoblotting . ere is a correlation between the titer of ANucA and intensity of reac: ion with nucleolar proteins in immunoblotting. HgCl2 also, induced market IgG and C3 renal deposits in A.SW mice. The incidence of these rena] immune deposits may be related to ANucA .
Treatment of A.SW mice with DP resulted in production of 10 titer of ANA, which started at 6 weeks from starting treatment, increased slowly and peaked at 16 - 18 weeks. These ANA reacted with 40 - 48 kD , 50 - 60 ] D and 80 - 88 kD nuclear proteins in immunoblotting . DP treatment also ind ced mild IgG &: C3 renal deposits in A.SW mice only after 18 weeks of treatm t .
In A.SW mice treated with both Hg02 and DP combined, high titers of ANucA and low titer of ANA. Both ANucA and AN reacted strongly with corresponding nucleolar and nuclear pro eins in immunoblotting . In the combined treatment, we also observe that DP
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potentiates ANucA titer induced by HgC12 at 2 weeks from tre HgCl2 caused early development of ANA by OP at 4 weeks and ANA titer at 10 weeks. A.SW mice treated with HgQ2 and OP co showed very marked IgG and C3 renal immune deposits.
DP pre-treatment of A.SW mice followed by HgCl2 injecti n caused potentiation of ANucA titer induced by HgCl2 after 2 weeks fr m HgCl2 treatment while at the end of treatment ( 8 weeks from HgCl2 t eatment ) there was significant reduction in both the ANA and ANucA titers. Also OP pre-treatment followed by HgCl2 treatment caused less se re renal pathologic lesions than HgCl2 alone in A.SW mice.
The initial treatment of A.SW mice with HgQ2 followed by DP treatment caused resistance to ANA induction by OP. After HgCl2 stop ing, the ANucA production continued as usual, peaked at 6 weeks aft starting HgQ2 treatment and started to decrease at 10 weeks and at 18 w eks , the ANucA is still relatively high.
The data showed in this work are consistent with the hypothesis at there is a final common pathway for the systemic autoimmunity induce by both HgCl2 and OP . Studying these experimental models make us ware of autoimmune adverse effects of these chemicals. Also, there a e certain analogies between chemical induced autoimmunity and certai human autoimmune diseases such as SLE and scleroderma. So , stud’ g this experimental system gives valuable information about ind regulation of autoimmune diseases and also may explain the me human autoimmune diseases that may have clinical relevance.