[Effects of dioxins on protein kinases and disruption of signal transduction pathways].
Dioxins(polychlorinated dibenzo-p-dioxins and related compounds, e.g. polychlorinated dibenzofurans and coplanar polychlorinated biphenyls) has been recognized as endocrine disruptors. Typical endocrine disrupting effects on human of dioxins were shown in 'Yusho' disease(mass PCB poisoning in Japan and Taiwan) patients. A major symptom was chloracne-like lesion on skin, indicating that growth on keratinocytes was stimulated by dioxins. In case of in utero exposure, the body weights of children were lowered, and in some case children had poorer cognitive development in Taiwan episode. Dioxins stimulate the expression of genes(e.g. cytochrome P450 1A1 and related drug metabolizing enzymes) via a ligand dependent transactivating factor, arylhydrocarbon receptor(Ah-R). Besides gene expression of drug metabolizing enzyme, down-regulation of epidermal growth factor receptor has been observed in tissue and cultured cells by exposure to TCDD. Alternative pathways for gene expression such as cross-talk between epidermal growth factor/MAP kinase pathway and Ah-R pathway are reviewed with respect to understanding the endocrine disrupting activity of dioxins.
Aoki
Y
Y
National Institute for Environmental Studies, Environmental Health Sciences Division.
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004147:Dioxins / Q000633:toxicity*; D015536:Down-Regulation; D004703:Endocrine System / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D004815:Epidermal Growth Factor / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000502:physiology
D004147:Dioxins; D004785:Environmental Pollutants; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D004815:Epidermal Growth Factor; D003577:Cytochrome P-450 Enzyme System; D011494:Protein Kinases