The Cutaneous Lesions of Dioxin Exposure: Lessons from the Poisoning of Victor Yushchenko

Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne" are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who...

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Bibliographic Details
Published in:	Toxicological sciences Vol. 125; no. 1; pp. 310 - 317
Main Authors:	Saurat, Jean-Hilaire, Kaya, Guerkan, Saxer-Sekulic, Nikolina, Pardo, Bruno, Becker, Minerva, Fontao, Lionel, Mottu, Florence, Carraux, Pierre, Pham, Xuan-Cuong, Barde, Caroline, Fontao, Fabienne, Zennegg, Markus, Schmid, Peter, Schaad, Olivier, Descombes, Patrick, Sorg, Olivier
Format:	Journal Article
Language:	English
Published:	United States Oxford University Press 01-01-2012
Subjects:	Biopsy Gene Expression - drug effects Gene Expression Profiling Hamartoma - chemically induced Hamartoma - genetics Hamartoma - pathology Hamartoma - therapy Humans Male Middle Aged Multimodal Imaging Polychlorinated Dibenzodioxins - pharmacokinetics Polychlorinated Dibenzodioxins - poisoning Positron-Emission Tomography Skin - drug effects Skin - metabolism Skin - pathology Skin Diseases - chemically induced Skin Diseases - genetics Skin Diseases - pathology Skin Diseases - therapy Tomography, X-Ray Computed Treatment Outcome toxicity skin dioxin morphology hamartoma
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Summary:	Several million people are exposed to dioxin and dioxin-like compounds, primarily through food consumption. Skin lesions historically called "chloracne" are the most specific sign of abnormal dioxin exposure and classically used as a key marker in humans. We followed for 5 years a man who had been exposed to the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), at a single oral dose of 5 million-fold more than the accepted daily exposure in the general population. We adopted a molecular medicine approach, aimed at identifying appropriate therapy. Skin lesions, which progressively covered up to 40% of the body surface, were found to be hamartomas, which developed parallel to a complete and sustained involution of sebaceous glands, with concurrent transcriptomic alterations pointing to the inhibition of lipid metabolism and the involvement of bone morphogenetic proteins signaling. Hamartomas created a new compartment that concentrated TCDD up to 10-fold compared with serum and strongly expressed the TCDD-metabolizing enzyme cytochrome P450 1A1, thus representing a potentially significant source of enzymatic activity, which may add to the xenobiotic metabolism potential of the classical organs such as the liver. This historical case provides a unique set of data on the human tissue response to dioxin for the identification of new markers of exposure in human populations. The herein discovered adaptive cutaneous response to TCDD also points to the potential role of the skin in the metabolism of food xenobiotics.
ISSN:	1096-6080 1096-0929
DOI:	10.1093/toxsci/kfr223