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© 1995 Oxford University Press

research-article

The Herbicide Dicamba (2-Methoxy-3,6-dichlorobenzoic Acid) Is a Peroxisome Proliferator in Rats1

P. ESPANDIARI*, V. A. THOMAS*, H. P. GLAUERT*,{dagger}, M. O'BRIEN{ddagger}, D. NOONAN*,{ddagger} and L. W. ROBERTSON*,2

*Graduate Center for Toxicology, University of Kentucky Lexington, Kentucky 40506-0054 {dagger}Department of Nutrition and Food Science, University of Kentucky Lexington, Kentucky 40506-0054 {ddagger}Department of Biochemistry, University of Kentucky Lexington, Kentucky 40506-0054

Received July 5, 1994; accepted November 18, 1994

The widely used broad leaf herbicide, dicamba, or Banvel, is similar in structure to xenobiotics which induce hepatic drug metabolism or proliferation of hepalic peroxisomes in rodents. The ability of xenobiotics to effect these hepatic changes often portends their positive outcomes in chronic bioassays. Dicamba's ability to induce hepatomegaly and peroxisome proliferation was studied in male and female Sprague-Dawley rats. Rats were placed on feed containing 0, 0.001, 0.01, 0.1, or 1% dicamba or 0.01% ciprofibrate for 3 weeks. Dicamba had no effect on relative liver weights or feed efficiency in either female or male rats at all doses tested. Dicamba, however, caused a statistically significant increase in peroxisomal ß-oxidation activity in liver homogenates from rats of both sexes fed 1% dicamba Fatty acyl CoA-oxidase activity was increased in male rats fed 1% dicamba. A protein of Mr 80 kDa was visible when liver homogenates of female or male rats fed 1% dicamba were subjected to SDS-PAGE. Lauric acid hydroxylase activity and CYP4A-reactive protein were increased in microsomes from male rats fed the highest level of dicamba. Moreover, dicamba was observed to transcriptionally upregulate the peroxisome proliferator-activated receptor (PPAR), a peroxisome proliferator sensitive receptor previously shown to be linked to the transcriptional regulation of a variety of peroxisome specific enzymes. These studies show that dicamba is a peroxisome proliferator in rats. Although dicamba was not an efficacious inducer of peroxisomal enzymes in these rats, dicamba's ability to transcriptionally activate the PPAR and induce peroxisomal and related enzymes must be considered in the safety evaluation of this herbicide.


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