Cellular Toxic Effects and Action Mechanisms Of 2,2', 4,6,6'-Pentachlorobiphenyl

  • Kim Sun-Hee (Department of Life Science, Division of Molecular and Life Science, and School of Environmental Science and Engineering, Pohang University of Science and Technology) ;
  • Shin Kum-Joo (Division of Biology, California Institute of Technology) ;
  • Kim Dohan (Department of Life Science, Division of Molecular and Life Science, and School of Environmental Science and Engineering, Pohang University of Science and Technology) ;
  • Kim Yun-Hee (Department of Life Science, Division of Molecular and Life Science, and School of Environmental Science and Engineering, Pohang University of Science and Technology) ;
  • Ryu Sung Ho (Department of Life Science, Division of Molecular and Life Science, and School of Environmental Science and Engineering, Pohang University of Science and Technology) ;
  • Suh Pann-Ghill (Department of Life Science, Division of Molecular and Life Science, and School of Environmental Science and Engineering, Pohang University of Science and Technology)
  • Published : 2004.07.01

Abstract

Polychlorinated biphenyls (PCBs), one a group of persistent and widespread environmental pollutants, have been considered to be involved in immunotoxicity, carcinogenesis, and apoptosis. However, the toxic effects and physical properties of a PCB congener are dependent on the structure. In the present study, we investigate the toxic effects and action mechanisms of PCBs In cells. Among the various congeners tested, 2,2',4,6,6'-PeCB-pentachlorobiphenyl (PeCB), a highly ortho-substituted congener having negligible binding affinity for aryl hydrocarbon receptor (AhR), caused the most potent toxicity and specific effects in several cell types. 2,2',4,6,6'-PeCB induced apoptotic cell death of human monocytic cells, suggesting that PCB-induced apoptosis may be linked to immunotoxicity. In addition, 2,2',4,6,6'-PeCB induced mitotic arrest by interfering with mitotic spindle assembly in NIH3T3 fibroblasts, followed by genetic instability which triggers p53 activation. Which suggests that 2,2',4,6,6'-PeCB may be involved in cancer development by causing genetic instability through mitotic spindle damage. On the other hand, 2,2',4,6,6'-PeCB increased cyclooxygenase-2 (COX-2) involved in cell survival through ERK1/2 MAPK and p53 in Rat-1 fibroblasts and mouse embryonic fibroblasts, triggering compensatory mechanism for abating its toxicity. Taken together, these results demonstrate that PCB congeners of different structure have distinct mechanism of action and 2,2',4,6,6'-PeCB causes several toxicity as well as compensatory mechanism in cells.

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