The Quest Of Mechanism Research On Chloracne Caused By Occupational Expose To Dioxins

Objective: Dioxins are a class of polychlorinated aromatic hydrocarbons of persistentenvironmental toxicity which are formed as an unwanted by-product in themanufacture of chlorinated hydrocarbons. Dioxins can elicit wide spectrum of toxicresponses in humans including reproductive, developmental and immunologictoxicities as well as carcinogenicity. It is the only skin effects of dioxin exposure,especially chloracne, which is considered to be one of the most specific and sensitivebiomarkers of dioxins intoxication. In the present study, we used QuantiTect SYBRGreen to measure the mRNA levels of AhR,CYP1A1,GSTA1,c-fos and TGF-αinhuman epidermis, who suffer chloracne. The goal is to clarify the effects of AhR,CYP1A1,GSTA1,c-fos and TGF-αon dioxin induced chloracne and to provide somesound proof for the further research in molecular mechanisms of chloracne.Methods: The disease group comes from man workers who suffer from chloracnedue to the process with pentachlorophenol sodium (Na-PCP) in a chemical plant inTianjin. Control group is chosen from normal people in Tianjin, who don't have suchkind of vocational history and contact history. The two groups have excellentcomparability in demography feature. To obey the "minimum wound" principle, thetoroidal skin samplers were used for both the disease group and the control group.Every piece of skin is 0.5×0.5 cm of diameter×depth and washed quickly in sodiumchloride after ex vivo, then preserved in liquid nitrogen. The SYBR Greenquantitative reverse transcription PCR-technique was used for the measurement of therelative transcription levels for the AhR, CYP1A1, GSTA1,c-fos and TGF-αmRNA ofepidermis.Results: Firstly, Basic demographic characteristic description: In this study, weinvestigated 12 people of chloracne as disease group, the average age is (52.08±7.62)year old; Control group, 12 people is formed by the average age of (51.42±5.30) yearold. The two groups have excellent comparability in age, Body mass index (BMI), thepercentage of smoking and drinking (P＞0.05). Secondly, the effect on the transcripts level of the AhR,CYP1A1,GSTA1,c-fos and TGF-αmRNA in human epidermis:Compared with the control group, AhR, CYP1A1, GSTA1 and c-fos transactivationwere induced in the skin of chloracne patients who are long-term expose to dioxins.These genes expression amount are significantly from the control group with the2.9-fold, 8.6-fold, 4.4-fold and 4.4-fold increase respectively (P＜0.05); while theTGF-αmRNA content of epidermis were increased without significant difference (P=0.082). Further analysis of the relevant relationship between the expression level ofAhR mRNA and CYP1A1mRNA, AhR mRNA and GSTA1 mRNA, AhR mRNA andc-fos mRNA showed that: there are no significant relevant relationships between theexpression level of AhR mRNA and CYP1A1mRNA, AhR mRNA and GSTA1 mRNAAhR mRNA and c-fos mRNA respectively in the control group; however, inchloracne group, the level of AhR mRNA and CYP1A1mRNA, AhR mRNA and c-fosmRNA exist highly positive relevance with the coefficient of 0.752 and 0.650(P=0.005, 0.002).Conclusion: AhR, CYP1A1, and GSTA1 were significantly up-regulated in the skin ofchloracne, and there is a strong positive correlation between AhR and CYP1A1mRNA expression. All these results strongly suggest that AhR/ARNTheterodimerization probably be a prerequisite of chloracne pathogenesis. Furtherstudy proved that long-term exposing to dioxin can increase the c-fos transactivationin the skin of chloracne, the level of AhR mRNA and c-fos mRNA exist highlypositive relevance. This induction may be through AhR by increasing SRC activity.The increasing of c-fos expression may disturb normal proliferation anddifferentiation of human epidermis cell, and lead to the form and persistence ofchlroacne.