Dioxin-induced chloracne – reconstructing the cellular and molecular mechanisms of a classic environmental disease

Authors


Andrey A. Panteleyev
Department of Dermatology
College of Physicians & Surgeons
Columbia University
630 West 168th Street
Vanderbilt Clinic VC-1526
New York, NY 10032
USA
Tel.: +1 212 305 7699
Fax: +1 212 305 7391
e-mail: ap374@columbia.edu

Abstract

Abstract:  2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is among the most toxic pollutants known to date that serves as a prototype for a group of halogenated hydrocarbon compounds characterized by extraordinary environmental persistence and unique ability to concentrate in animal and human tissues. TCDD can elicit a complex array of pleiotropic adverse effects in humans, although chloracne, a specific type of acne-like skin disease, is the only consistent manifestation of dioxin intoxication, thus representing a ‘hallmark’ of TCDD exposure. Chloracne is considered to be one of the most specific and sensitive biomarkers of TCDD intoxication that allows clinical and epidemiological evaluation of exposure level at threshold doses. The specific cellular and molecular mechanisms involved in pathogenesis of chloracne are still unknown. In this review, we summarize the available clinical data on chloracne and recent progress in understanding the role of the dioxin-dependent pathway in the control of gene transcription and discuss molecular and cellular events potentially involved in chloracne pathogenesis. We propose that the dioxin-induced activation of skin stem cells and a shift in differentiation commitment of their progeny may represent a major mechanism of chloracne development.

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