The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a peroxisome proliferator in rats

P Espandiari; V A Thomas; H P Glauert; M O'Brien; D Noonan; L W Robertson

doi:10.1006/faat.1995.1077

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Journal article

The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a peroxisome proliferator in rats

P Espandiari, V A Thomas, H P Glauert, M O'Brien, D Noonan and L W Robertson

Fundamental and applied toxicology, Vol.26(1), pp.85-90

06/1995

DOI: 10.1006/faat.1995.1077

PMID: 7657066

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Abstract

The widely used broad leaf herbicide, dicamba, or Banvel, is similar in structure to xenobiotics which induce hepatic drug metabolism or proliferation of hepatic 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 beta-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 M(r) 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.

Body Weight - drug effects

Cytochrome P-450 Enzyme System - metabolism

Microbodies - metabolism

Molecular Sequence Data

Male

Mixed Function Oxygenases - metabolism

Clofibric Acid - toxicity

Dose-Response Relationship, Drug

Clofibric Acid - analogs & derivatives

Liver - drug effects

Acyl-CoA Oxidase

Base Sequence

Female

Fibric Acids

Microsomes, Liver - enzymology

Microbodies - enzymology

Cytochrome P-450 CYP4A

Oxidation-Reduction

Oxidoreductases - metabolism

Dicamba - toxicity

Liver - metabolism

Microbodies - drug effects

Rats

Rats, Sprague-Dawley

Transcription Factors - metabolism

Organ Size - drug effects

Animals

Clofibric Acid - metabolism

Dicamba - metabolism

Receptors, Cytoplasmic and Nuclear - metabolism

Details

Title: Subtitle: The herbicide dicamba (2-methoxy-3,6-dichlorobenzoic acid) is a peroxisome proliferator in rats
Creators: P Espandiari - Department of Nutrition and Food Science, University of Kentucky, Lexington 40506-0054, USA
V A Thomas
H P Glauert
M O'Brien
D Noonan
L W Robertson
Resource Type: Journal article
Publication Details: Fundamental and applied toxicology, Vol.26(1), pp.85-90
Publisher: United States
DOI: 10.1006/faat.1995.1077
PMID: 7657066
ISSN: 0272-0590
eISSN: 1095-6832
Grant note: CA-43719 / NCI NIH HHS U07/CCU40835 / PHS HHS CA-01688 / NCI NIH HHS
Language: English
Date published: 06/1995
Academic Unit: Occupational and Environmental Health
Record Identifier: 9984002315602771

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