Expression of AhR, CYP1A1, GSTA1, c-fos and TGF-alpha 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.
Tang
Nai-Jun
NJ
The College of Environmental Science and Engineering, Nankai University, Weijin Road 94#, Tianjin 300071, China. tangnaijun@tijmu.edu.cn
Liu
Jing
J
Coenraads
P J
PJ
Dong
Li
L
Zhao
Li-Jun
LJ
Ma
Shi-Wei
SW
Chen
Xi
X
Zhang
Chun-Mei
CM
Ma
Xiao-Ming
XM
Wei
Wen-Guo
WG
Zhang
Peng
P
Bai
Zhi-Peng
ZP
D054506:Chloracne / Q000209:etiology* / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D016762:Genes, fos; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D016211:Transforming Growth Factor alpha; D019363:Cytochrome P-450 CYP1A1; C484555:GSTA1 protein, human; D005982:Glutathione Transferase