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- Title
INDUCTION OF HEPATIC CYTOCHROME P4501A1/2B ACTIVITY AND DISRUPTION OF THYROGLOBULIN SYNTHESIS/SECRETION BY MONO-ortho POLYCHLORINATED BIPHENYL AND ITS HYDROXYLATED METABOLITES IN RAT CELL LINE.
- Authors
Fangxing Yang; Ying Xu; Hongmei Pan; Desheng Wu
- Abstract
As the active metabolites of polychlorinated biphenyl (PCBs), hydroxylated polychlorinated biphenyls (OH-PCBs) are found in wildlife and human tissues. They have been proposed as main contributors for endocrine disruption of PCBs in living organisms. In this study, mono-ortho PCB 156 and its hydroxylated metabolites 4'-OH-PCB 159, 4'-OH-PCB 121, and 4'-OHPCB 72 were selected to investigate the toxic effects on rat hepatoma H4IIE cell line and rat thyroid follicle FRTL-5 cell line at concentrations of 1, 10², 104 nM. 7-Ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-dealkylase (PROD) activities were determined with micro-EROD/PROD to indicate cytochrome P4501A1 (CYP1A1) and cytochrome P4502B (CYP2B) induction in the H4IIE cell after exposure for 72 h. To assess thyroid disruption of these compounds, thyroglobulin concentrations also were detected inside FRTL-5 cell with immunocellularchemistry and in its medium with radioimmunoassay after exposure for 24 h. Significant inductions of EROD activity by PCB156 at 10² and 104 nM (p < 0.05) were observed, but no effects by the three OHPCBs in H4IIE cell line. 7-Pentoxyresorufin-O-dealkylase activities were induced only by 104 nM of PCB156 and the three OHPCBs (p < 0.05). Meanwhile, significant increases of thyroglobulin concentrations were observed in the medium of FRTL-5 cell exposed to 4'-OH-PCB 121 and 4'-OH-PCB 72 at all of the test concentrations (p < 0.05), but not to the other compounds. The results demonstrated that mono-ortho PCBs mainly could be metabolized to hydroxylated metabolites through CYP1A1 instead of CYP2B. Moreover, after being metabolized, OH-PCBs still sustained the ability to induce PROD activity and did exhibit the disruption on thyroglobulin synthesis/excretion in rat cells.
- Publication
Environmental Toxicology & Chemistry, 2008, Vol 27, Issue 1, p220
- ISSN
0730-7268
- Publication type
Academic Journal
- DOI
10.1897/07-108.1