The effects of dietary dicamba (1918009) on the induction of hepatic peroxisomal and microsomal enzymes were investigated in rats. Sprague-Dawley-rats were divided into groups of six rats each based on body weight, and given a diet which included dicamba at concentrations of 0.001, 0.01, 0.1, or 1%. A diet containing 0.01% ciprofibrate was used as a control. Body weight and feed intake were monitored. The rats were killed at 3 weeks and livers were removed. Hepatic subcellular fractions were prepared, and the protein concentration of each fraction was determined. Catalase, fatty-acyl-coenzyme-A-oxidase (FAO), and total peroxisomal beta oxidation activities were determined. In addition, microsomal cytochrome-P450 content, rates of microsomal O-dealkylation of ethoxyresorufin and benzyloxyresorufin, cytochrome-P450 1A and 2B activities, and hepatic microsomal lauric-acid-hydroxylase were determined. Mammalian cell cotransfections were performed. All dicamba treatments did not result in any changes in body weight gain or liver weight. Feed efficiency was not altered. Dicamba treatment at 1% increased FAO activity in male rats, peroxisomal beta oxidation, lauric-acid-hydroxylase activity, and CYP4A reactive protein in female and male rats, and yielded an 80 kilodalton protein as indicated by gel electrophoresis. Other parameters were not changed by dicamba treatment. Ciprofibrate increased liver weights, lauric-acid-hydroxylase activity, and P4504A protein, but did not affect any other parameter. Dicamba upregulated transcription of an FAO driven reporter gene with half maximal stimulation at 0.2 millimolar. The authors conclude that dicamba at a 1% dietary level yielded weak or moderate increases in peroxisomal enzymes, and in CYP4A content and activity. Dicamba also caused peroxisome proliferator activated receptor activation.
University of Kentucky, Department of Preventive Medicine, Lexington, KY