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Hexabromocyclododecane decreases tumor-cell-binding capacity and cell-surface protein expression of human natural killer cells.

Abstract
Hexabromocyclododecane (HBCD) is a flame retardant that decreases the lytic function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. Thus, HBCD has the potential to increase cancer incidence and viral infections. NK cells must bind to their targets for lysis to occur. Thus, concentrations of HBCD that decrease lytic function were examined for their ability to alter NK binding to tumor targets. Levels of HBCD that caused a loss of binding function were examined for effects on expression of cell surface proteins needed for binding. NK cells exposed to HBCD for 24 h, 48 h or 6 days or to HBCD for 1 h followed by 24 h, 48 h or 6 days in HBCD-free media were examined for binding function and cell surface protein expression. The results indicated that exposure of NK cells to 10 microM HBCD for 24 h (which caused a greater than 90% loss of lytic function) caused a very significant decrease in NK cell binding function (70.9%), and in CD16 and CD56 cell-surface protein expression (57.8 and 24.6% respectively). NK cells exposed to 10 microM HBCD for 1 h followed by 24 h in HBCD-free media (which caused a 89.3% loss of lytic function) showed decreased binding function (79.2%), and CD 16 expression (48.1%). Results indicate that HBCD exposures decreased binding function as well as cell-surface marker expression in NK cells and that these changes may explain the losses of lytic function induced by certain HBCD exposures.
AuthorsNatasha C Hinkson, Margaret M Whalen
JournalJournal of applied toxicology : JAT (J Appl Toxicol) Vol. 30 Issue 4 Pg. 302-9 (May 2010) ISSN: 1099-1263 [Electronic] England
PMID19938002 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright2009 John Wiley & Sons, Ltd.
Chemical References
  • Antigens, Surface
  • CD56 Antigen
  • FCGR3B protein, human
  • Flame Retardants
  • GPI-Linked Proteins
  • Hydrocarbons, Brominated
  • Receptors, IgG
  • hexabromocyclododecane
Topics
  • Antigens, Surface (biosynthesis)
  • CD56 Antigen (biosynthesis)
  • Cell Culture Techniques
  • Cell Survival (drug effects)
  • Coculture Techniques
  • Cytotoxicity Tests, Immunologic
  • Cytotoxicity, Immunologic (drug effects)
  • Dose-Response Relationship, Drug
  • Female
  • Flame Retardants (toxicity)
  • Flow Cytometry
  • GPI-Linked Proteins
  • Humans
  • Hydrocarbons, Brominated (toxicity)
  • K562 Cells
  • Killer Cells, Natural (drug effects, immunology, metabolism)
  • Male
  • Receptors, IgG (biosynthesis)
  • Time Factors

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