title: The cutaneous lesions of dioxin exposure: lessons from the poisoning of Victor Yushchenko.
abstract: 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.
authors: Swiss Centre for Applied Human Toxicology, Dermatotoxicology Unit, University of Geneva, 1211 Geneva 4, Switzerland. jean.saurat@unige.ch
authors: Jean-Hilaire
authors: JH
authors: Saurat
authors: Guerkan
authors: G
authors: Kaya
authors: Nikolina
authors: N
authors: Saxer-Sekulic
authors: Bruno
authors: B
authors: Pardo
authors: Minerva
authors: M
authors: Becker
authors: Lionel
authors: L
authors: Fontao
authors: Florence
authors: F
authors: Mottu
authors: Pierre
authors: P
authors: Carraux
authors: Xuan-Cuong
authors: XC
authors: Pham
authors: Caroline
authors: C
authors: Barde
authors: Fabienne
authors: F
authors: Fontao
authors: Markus
authors: M
authors: Zennegg
authors: Peter
authors: P
authors: Schmid
authors: Olivier
authors: O
authors: Schaad
authors: Patrick
authors: P
authors: Descombes
authors: Olivier
authors: O
authors: Sorg
mesh_terms: D001706:Biopsy; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006222:Hamartoma / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000506:poisoning*; D049268:Positron-Emission Tomography; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000072317:Polychlorinated Dibenzodioxins