Time-dependent autoimmune response of dichloroacetyl chloride in female MRL +/+ mice

We have reported that trichloroethene (TCE) and dichloroacetyl chloride (DCAC, one of the metabolites of TCE) can induce autoimmune response in female MRL +/+ mice; however, the response of DCAC was much more pronounced. To understand if This DCAC-induced autoimmune response is time dependent, the following studies were conducted. Female MRL +/+ mice (5 weeks old) received i.p. injections of 0.2 mmol/kg of DCAC in corn oil (100 M or an equal volume of vehicle (controls) every 4th day. The animals were euthanized 24 hr following 2, 4, 6 and 8 weeks (W) of treatments. Sera and major tissues were collected and analyzed; ELISA kits were used to measure autoantibodies in the sera. Spleen weight showed consistent increases in the DCAC-treated animals at 4, 6 and 8 weeks of treatment. Serum IgG increased by 326, 280 and 1 75% at 4, 6 and 8 weeks, respectively. The following pattern of autoimmune responses was observed in the sera of DCAC-treated mice: anti nuclear antibodies: 4W, 0/4; 6W, 3/5; 8W, 1/5; anti-ssDNA antibodies: 4W, 1/4; 6W, 4/5; 8W, 4/5; anti-cardiolipin antibodies: 4W, 3/4; 6W, 4/5; 8W. 1/5; DCAC-specific antibodies: 4W, 1/4; 6W, 5/5 and 8W, 3/5. No changes were observed at 2 weeks of DCAC treatment. Thus, six weeks of treatment provides an optimal autoimmune response at 0.2 mmol/kg of DCAC. These studies along with dose-response studies should form a basis for future in-depth studies towards understanding of TCE and/or DCAC-induced autoimmune response.