Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity
Identifieur interne : 000C33 ( Main/Exploration ); précédent : 000C32; suivant : 000C34Trichloroethylene: Parkinsonism and complex 1 mitochondrial neurotoxicity
Auteurs : Don M. Gash [États-Unis] ; Kathryn Rutland [États-Unis] ; Naomi L. Hudson [États-Unis] ; Patrick G. Sullivan [États-Unis] ; Guoying Bing [États-Unis] ; Wayne A. Cass [États-Unis] ; Jignesh D. Pandya [États-Unis] ; Mei Liu [États-Unis] ; Dong-Yong Choi [États-Unis] ; Randy L. Hunter [États-Unis] ; Greg A. Gerhardt [États-Unis] ; Charlie D. Smith [États-Unis] ; John T. Slevin [États-Unis] ; T. Scott Prince [États-Unis]Source :
- Annals of Neurology [ 0364-5134 ] ; 2008-02.
Abstract
Objective: To analyze a cluster of 30 industrial coworkers with Parkinson's disease and parkinsonism subjected to long‐term (8–33 years) chronic exposure to trichloroethylene. Methods: Neurological evaluations were conducted on the 30 coworkers, including a general physical and neurological examination and the Unified Parkinson's Disease Rating Scale. In addition, fine motor speed was quantified and an occupational history survey was administered. Next, animal studies were conducted to determine whether trichloroethylene exposure is neurotoxic to the nigrostriatal dopamine system that degenerates in Parkinson's disease. The experiments specifically analyzed complex 1 mitochondrial neurotoxicity because this is a mechanism of action of other known environmental dopaminergic neurotoxins. Results: The three workers with workstations adjacent to the trichloroethylene source and subjected to chronic inhalation and dermal exposure from handling trichloroethylene‐soaked metal parts had Parkinson's disease. Coworkers more distant from the trichloroethylene source, receiving chronic respiratory exposure, displayed many features of parkinsonism, including significant motor slowing. Neurotoxic actions of trichloroethylene were demonstrated in accompanying animal studies showing that oral administration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons. Interpretation: Trichloroethylene, used extensively in industry and the military and a common environmental contaminant, joins other mitochondrial neurotoxins, MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and some pesticides, as a risk factor for parkinsonism. Ann Neurol 2007
Url:
DOI: 10.1002/ana.21288
Affiliations:
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Sullivan</name></author><author><name sortKey="Bing, Guoying" sort="Bing, Guoying" uniqKey="Bing G" first="Guoying" last="Bing">Guoying Bing</name></author><author><name sortKey="Cass, Wayne A" sort="Cass, Wayne A" uniqKey="Cass W" first="Wayne A." last="Cass">Wayne A. Cass</name></author><author><name sortKey="Pandya, Jignesh D" sort="Pandya, Jignesh D" uniqKey="Pandya J" first="Jignesh D." last="Pandya">Jignesh D. Pandya</name></author><author><name sortKey="Liu, Mei" sort="Liu, Mei" uniqKey="Liu M" first="Mei" last="Liu">Mei Liu</name></author><author><name sortKey="Choi, Dong Ong" sort="Choi, Dong Ong" uniqKey="Choi D" first="Dong-Yong" last="Choi">Dong-Yong Choi</name></author><author><name sortKey="Hunter, Randy L" sort="Hunter, Randy L" uniqKey="Hunter R" first="Randy L." last="Hunter">Randy L. Hunter</name></author><author><name sortKey="Gerhardt, Greg A" sort="Gerhardt, Greg A" uniqKey="Gerhardt G" first="Greg A." last="Gerhardt">Greg A. 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Gash</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Rutland, Kathryn" sort="Rutland, Kathryn" uniqKey="Rutland K" first="Kathryn" last="Rutland">Kathryn Rutland</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>College of Public Health, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Hudson, Naomi L" sort="Hudson, Naomi L" uniqKey="Hudson N" first="Naomi L." last="Hudson">Naomi L. Hudson</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Sullivan, Patrick G" sort="Sullivan, Patrick G" uniqKey="Sullivan P" first="Patrick G." last="Sullivan">Patrick G. Sullivan</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Bing, Guoying" sort="Bing, Guoying" uniqKey="Bing G" first="Guoying" last="Bing">Guoying Bing</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Cass, Wayne A" sort="Cass, Wayne A" uniqKey="Cass W" first="Wayne A." last="Cass">Wayne A. Cass</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Pandya, Jignesh D" sort="Pandya, Jignesh D" uniqKey="Pandya J" first="Jignesh D." last="Pandya">Jignesh D. Pandya</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Liu, Mei" sort="Liu, Mei" uniqKey="Liu M" first="Mei" last="Liu">Mei Liu</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Choi, Dong Ong" sort="Choi, Dong Ong" uniqKey="Choi D" first="Dong-Yong" last="Choi">Dong-Yong Choi</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Hunter, Randy L" sort="Hunter, Randy L" uniqKey="Hunter R" first="Randy L." last="Hunter">Randy L. Hunter</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Gerhardt, Greg A" sort="Gerhardt, Greg A" uniqKey="Gerhardt G" first="Greg A." last="Gerhardt">Greg A. Gerhardt</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Neurology, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Smith, Charlie D" sort="Smith, Charlie D" uniqKey="Smith C" first="Charlie D." last="Smith">Charlie D. Smith</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Anatomy and Neurobiology, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Neurology, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Slevin, John T" sort="Slevin, John T" uniqKey="Slevin J" first="John T." last="Slevin">John T. Slevin</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>The Morris K. Udall Parkinson's Disease Research Center of Excellence, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>Department of Neurology, College of Medicine, University of Kentucky, Lexington</wicri:cityArea></affiliation></author><author><name sortKey="Prince, T Scott" sort="Prince, T Scott" uniqKey="Prince T" first="T. Scott" last="Prince">T. Scott Prince</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><placeName><region type="state">Kentucky</region></placeName><wicri:cityArea>College of Public Health, University of Kentucky, Lexington</wicri:cityArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Neurology</title><title level="j" type="abbrev">Ann Neurol.</title><idno type="ISSN">0364-5134</idno><idno type="eISSN">1531-8249</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2008-02">2008-02</date><biblScope unit="volume">63</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="184">184</biblScope><biblScope unit="page" to="192">192</biblScope></imprint><idno type="ISSN">0364-5134</idno></series><idno type="istex">7386906DB45C6617E236752F3F58C8A8FB7295FF</idno><idno type="DOI">10.1002/ana.21288</idno><idno type="ArticleID">ANA21288</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0364-5134</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Objective: To analyze a cluster of 30 industrial coworkers with Parkinson's disease and parkinsonism subjected to long‐term (8–33 years) chronic exposure to trichloroethylene. Methods: Neurological evaluations were conducted on the 30 coworkers, including a general physical and neurological examination and the Unified Parkinson's Disease Rating Scale. In addition, fine motor speed was quantified and an occupational history survey was administered. Next, animal studies were conducted to determine whether trichloroethylene exposure is neurotoxic to the nigrostriatal dopamine system that degenerates in Parkinson's disease. The experiments specifically analyzed complex 1 mitochondrial neurotoxicity because this is a mechanism of action of other known environmental dopaminergic neurotoxins. Results: The three workers with workstations adjacent to the trichloroethylene source and subjected to chronic inhalation and dermal exposure from handling trichloroethylene‐soaked metal parts had Parkinson's disease. Coworkers more distant from the trichloroethylene source, receiving chronic respiratory exposure, displayed many features of parkinsonism, including significant motor slowing. Neurotoxic actions of trichloroethylene were demonstrated in accompanying animal studies showing that oral administration of trichloroethylene for 6 weeks instigated selective complex 1 mitochondrial impairment in the midbrain with concomitant striatonigral fiber degeneration and loss of dopamine neurons. Interpretation: Trichloroethylene, used extensively in industry and the military and a common environmental contaminant, joins other mitochondrial neurotoxins, MPTP (1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine) and some pesticides, as a risk factor for parkinsonism. Ann Neurol 2007</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Kentucky</li></region></list><tree><country name="États-Unis"><region name="Kentucky"><name sortKey="Gash, Don M" sort="Gash, Don M" uniqKey="Gash D" first="Don M." last="Gash">Don M. Gash</name></region><name sortKey="Bing, Guoying" sort="Bing, Guoying" uniqKey="Bing G" first="Guoying" last="Bing">Guoying Bing</name><name sortKey="Cass, Wayne A" sort="Cass, Wayne A" uniqKey="Cass W" first="Wayne A." last="Cass">Wayne A. Cass</name><name sortKey="Cass, Wayne A" sort="Cass, Wayne A" uniqKey="Cass W" first="Wayne A." last="Cass">Wayne A. Cass</name><name sortKey="Choi, Dong Ong" sort="Choi, Dong Ong" uniqKey="Choi D" first="Dong-Yong" last="Choi">Dong-Yong Choi</name><name sortKey="Gash, Don M" sort="Gash, Don M" uniqKey="Gash D" first="Don M." last="Gash">Don M. Gash</name><name sortKey="Gerhardt, Greg A" sort="Gerhardt, Greg A" uniqKey="Gerhardt G" first="Greg A." last="Gerhardt">Greg A. Gerhardt</name><name sortKey="Gerhardt, Greg A" sort="Gerhardt, Greg A" uniqKey="Gerhardt G" first="Greg A." last="Gerhardt">Greg A. Gerhardt</name><name sortKey="Gerhardt, Greg A" sort="Gerhardt, Greg A" uniqKey="Gerhardt G" first="Greg A." last="Gerhardt">Greg A. Gerhardt</name><name sortKey="Hudson, Naomi L" sort="Hudson, Naomi L" uniqKey="Hudson N" first="Naomi L." last="Hudson">Naomi L. Hudson</name><name sortKey="Hunter, Randy L" sort="Hunter, Randy L" uniqKey="Hunter R" first="Randy L." last="Hunter">Randy L. Hunter</name><name sortKey="Liu, Mei" sort="Liu, Mei" uniqKey="Liu M" first="Mei" last="Liu">Mei Liu</name><name sortKey="Pandya, Jignesh D" sort="Pandya, Jignesh D" uniqKey="Pandya J" first="Jignesh D." last="Pandya">Jignesh D. Pandya</name><name sortKey="Prince, T Scott" sort="Prince, T Scott" uniqKey="Prince T" first="T. Scott" last="Prince">T. Scott Prince</name><name sortKey="Rutland, Kathryn" sort="Rutland, Kathryn" uniqKey="Rutland K" first="Kathryn" last="Rutland">Kathryn Rutland</name><name sortKey="Slevin, John T" sort="Slevin, John T" uniqKey="Slevin J" first="John T." last="Slevin">John T. Slevin</name><name sortKey="Slevin, John T" sort="Slevin, John T" uniqKey="Slevin J" first="John T." last="Slevin">John T. Slevin</name><name sortKey="Smith, Charlie D" sort="Smith, Charlie D" uniqKey="Smith C" first="Charlie D." last="Smith">Charlie D. Smith</name><name sortKey="Smith, Charlie D" sort="Smith, Charlie D" uniqKey="Smith C" first="Charlie D." last="Smith">Charlie D. Smith</name><name sortKey="Sullivan, Patrick G" sort="Sullivan, Patrick G" uniqKey="Sullivan P" first="Patrick G." last="Sullivan">Patrick G. Sullivan</name><name sortKey="Sullivan, Patrick G" sort="Sullivan, Patrick G" uniqKey="Sullivan P" first="Patrick G." last="Sullivan">Patrick G. 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