Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-α in skin lesions from dioxin-exposed humans with chloracne

Occupational exposure to certain polychlorinated aromatic hydrocarbons such as dioxins has been suggested to cause chloracne which is a kind of skin disease. The molecular mechanisms of dioxin-mediated chloracne have not been clarified. It is possible that dioxins contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription and downstream genes such as CYP1A1, GSTA1 and TGF-alpha. The study on genes was through chloracne lesional skin, which has rarely been reported on previously. The expression levels of key genes, such as AhR, CYP1A1, GSTA1, c-fos and TGF-alpha in human epidermal tissue of chloracne cases and controls were detected by real-time PCR. Compared with controls, AhR, CYP1A1, GSTA1 and c-fos transactivations were significantly induced in the skins of chloracne patients who had long-term exposure to dioxins and dibenzofuranes. The TGF-alpha mRNA content of epidermal tissue was increased, but not significantly compared with controls. The study demonstrates that constitutive activation of the AhR pathway is probably a prerequisite of chloracne pathogenesis. The changes of genes expression may disturb normal proliferation and differentiation of human epidermis cells, and then lead to chloracne. (C) 2008 Elsevier Ireland Ltd. All rights reserved.