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Organochlorine pesticides induce epithelial to mesenchymal transition of human primary cultured hepatocytes
- Source :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 50(11)
- Publication Year :
- 2012
-
Abstract
- Persistent organic pollutants (POPs) are a group of organic or chemicals that adversely affect human health and are persistent in the environment. These highly toxic compounds include industrial chemicals, pesticides such as organochlorines, and unwanted wastes such as dioxins. Although studies have described the general toxicity effects of organochlorine pesticides, the mechanisms underlying its potential carcinogenic effects in the liver are not well understood. In this study, we analyzed the effect of three organochlorine pesticides (dichlorodiphenyltrichloroethane, heptachlore and endosulfan) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the epithelial to mesenchymal transition (EMT) in primary cultured human hepatocytes. We found that these compounds modified the hepatocyte phenotype, inducing cell spread, formation of lamellipodia structures and reorganization of the actin cytoskeleton in stress fibers. These morphological alterations were accompanied by disruption of cell-cell junctions, E-cadherin repression and albumin down-regulation. Interestingly, these characteristic features of dedifferentiating hepatocytes were correlated with the gain of expression of various mesenchymal genes, including vimentin, fibronectin and its receptor ITGA5. These various results show that organochlorines and TCDD accelerate cultured human hepatocyte dedifferentiation and EMT processes. These events could account, at least in part, for the carcionogenic and/or fibrogenic activities of these POPs.
- Subjects :
- medicine.medical_specialty
Epithelial-Mesenchymal Transition
Polychlorinated Dibenzodioxins
Vimentin
Toxicology
DDT
Heptachlor
Internal medicine
medicine
Hydrocarbons, Chlorinated
Humans
Epithelial–mesenchymal transition
Pesticides
Carcinogen
Cells, Cultured
Cytoskeleton
Persistent organic pollutant
biology
Chemistry
Mesenchymal stem cell
General Medicine
Actin cytoskeleton
Cadherins
Cell biology
Fibronectins
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Hepatocyte
Toxicity
biology.protein
Carcinogens
Hepatocytes
Endosulfan
Food Science
Subjects
Details
- ISSN :
- 18736351
- Volume :
- 50
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
- Accession number :
- edsair.doi.dedup.....9b434927d9532211131b76ee0137c436