Severe 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD) intoxication: Search for human serum biomarkers using 2D electrophoresis based proteomic analysis
2005
Abraham, K. | Brandenburger, L. | Meckert, C. | Ittrich, C. | Kopp-Schneider, A. | Krause, E. | Lamer, S. | Geusau, A. | Gundert-Remy, U. | Oberemm, A.
allemand. In 1997, two young women were highly exposed to TCDD at workplace in an unknown manner. The more intoxicated subject 1 suffered for a severe generalised chloracne, while subject 2 only had mild facial acne lesions (initial TCDD serum concentrations: 144 000 and 26 000 pg/g blood fat, respectively). Laboratory parameters were found to be mainly within the normal range apart from initially observed elevated blood lipids, leukocytosis and anemia in subject 1 (EHP 2001, 109:865). CYP 1A2 activity as measured by caffeine metabolism was found to be the only yet identified biomarker of response showing an up to 10-fold increase compared to controls (CPT 2002, 72:163).Changes in the serum protein expression pattern were explored by a proteomic approach (Toxicology 2004, doi:10.1016/j.tox.2004.06.061). Serum samples of both subjects taken in 1998, 2000 and 2002, respectively, were compared to samples from 6 healthy, age-matched women serving as controls. After removal of albumin and gamma-globulins (sample preparation kit; Amersham Biosciences), remaining serum proteins were separated using 2D gel electrophoresis. Fluorescently labelled gels (4 replicates per sample) were digitized using ProXpress imager. Image series were analyzed using ProteinMine¶® image analysis software in order to detect spots differentially expressed in both TCDD exposed and control subjects. Very few spots were found to be not present in one of the groups. Compared to these, a higher number of spots was found to be higher or lower expressed in one of the groups (median fold change: higher than 2 and lower than 0.5, respectively). Protein identification by MALDI-mass spectrometry revealed proteins which in part are known to be up-regulated during acute phase reaction. These findings may give insights into TCDD's mechanisms of action explaining for clinically relevant observations.
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Editeur Springer
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