Activation of Hepatic NF-κB by the Herbicide Dicamba (2-methoxy-3,6-dichlorobenzoic acid) in Female and Male Rats

Nuclear factor-KB is a transcription factor that is activated in many different cell types by pathologic stimuli, such as reactive oxygen intermediates. One class of hepatocarcinogens, the peroxisome proliferators, may produce reactive oxygen intermediates, and one potent peroxisome proliferator, ciprofibrate, was recently reported to activate nuclear factor-κB. In this study, we investigated whether Dicamba, a broad leaf herbicide and peroxisome proliferator, could activate nuclear factor-κB in the livers of rats. Female and male Sprague Dawley rats (n = 4) were fed diets containing either 0,1, or 3% Dicamba or 0.01% ciprofibrate for 7 days. As expected, the potent peroxisome proliferator, ciprofibrate, significantly increased fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities in male rats and, except for catalase, also in female rats. Dicamba significantly increased peroxisomal fatty acyl CoA oxidase, peroxisomal β-oxidation, and catalase activities, but decreased the activity of the cytosolic antioxidant enzyme, Se-dependent glutathione peroxidase, in both female and male rats. Dicamba increased nuclear factor-κB binding in the nuclear protein of livers from male rats fed both the 1 and 3% Dicamba diets. However, the highest binding was seen in nuclear protein from female rats fed 3% Dicamba. Both supershift and cold competition assays confirmed that this DNA binding activity was specific for nuclear factor-κB. Our results in this study suggest that the herbicide and peroxisome proliferator Dicamba has the ability to activate nuclear factor-κB.