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Related Experiment Videos

Butyltin exposure causes a rapid decrease in cyclic AMP levels in human lymphocytes.

M M Whalen1, B G Loganathan

  • 1Department of Chemistry, Tennessee State University, Nashville, Tennessee 37209, USA.

Toxicology and Applied Pharmacology
|March 13, 2001
PubMed
Summary

Butyltins (BTs), like tributyltin (TBT) and dibutyltin (DBT), impair natural killer (NK) cell function. These environmental toxins rapidly reduce NK cell cytotoxicity and cAMP levels, potentially increasing cancer and infection risks.

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Area of Science:

  • Environmental Toxicology
  • Immunology
  • Cellular Biology

Background:

  • Natural killer (NK) cells are crucial lymphocytes for innate immunity, eliminating tumor cells, virally infected cells, and antibody-coated cells.
  • Butyltins (BTs), including tributyltin (TBT) and dibutyltin (DBT), are environmental contaminants found in various consumer products and food sources.
  • BT exposure is linked to increased risks of cancer and viral infections, possibly due to impaired immune cell function.

Purpose of the Study:

  • To investigate the impact of tributyltin (TBT) and dibutyltin (DBT) exposure on the cytotoxic function and intracellular signaling pathways of natural killer (NK) cells.
  • To determine the dose- and time-dependent effects of BTs on NK cell activity and cellular energy levels.

Main Methods:

  • NK cells were exposed to varying concentrations of TBT and DBT for different durations (1-hour and 24-hour).

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  • Cytotoxic function of NK cells was measured.
  • Intracellular adenosine triphosphate (ATP) and cyclic adenosine monophosphate (cAMP) levels were quantified following BT exposure.

    • Main Results:

    • Exposure to 200 nM TBT or 1.5 µM DBT for 24 hours significantly reduced NK cell cytotoxic function by over 90%.
    • Even 1-hour exposure to higher concentrations of TBT and DBT (>90% reduction) markedly impaired NK cell cytotoxicity.
    • A 24-hour exposure decreased intracellular ATP levels by approximately 30%, while a 5-minute exposure to TBT or DBT caused an 80% reduction in cAMP levels.

    Conclusions:

    • Butyltins rapidly inhibit NK cell cytotoxic activity, potentially mediated by a swift decrease in intracellular cAMP levels.
    • ATP depletion is a longer-term effect of BT exposure on NK cells.
    • These findings suggest that BT-induced NK cell dysfunction may contribute to the increased susceptibility to cancer and viral infections observed in exposed individuals.