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Updated: Jul 16, 2026
Analysis of Human Natural Killer Cell Metabolism
Published on: June 22, 2020
Effect of dibutyltin on ATP levels in human natural killer cells
Fred D Dudimah1, Constance Gibson, Margaret M Whalen
1Department of Biological Sciences, Tennessee State University, Nashville, Tennessee 37209, USA.
Abstract:
This study investigates the role that decreased ATP levels may play in dibutyltin (DBT)-induced decreases in the tumor-cell-lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes capable of killing tumor cells, virally infected cells, and antibody coated cells. DBT is used as stabilizer in PVC plastics and has also been used as a deworming product in poultry. NK cells were exposed to various concentrations of DBT for 1 h, 24 h, 48 h, and 6 days before determining ATP levels and lytic function. ATP levels and lytic function were also determined in NK cells that were exposed to DBT for 1 h followed by 24 h, 48 h, and 6 days in DBT-free media. The results indicated that exposure of NK cells to 10 muM DBT for 1 h did not cause any significant decrease in NK cell ATP levels but did cause a very significant loss in lytic function. NK cells exposed to 500 nM DBT for 24 h showed significant loss of lytic function but showed no decrease in ATP levels. However, 48 h and 6 days exposures to those concentrations of DBT that caused decreases in tumor lysing function also caused significant decreases in ATP levels. Exposures of NK cells to varying DBT concentrations for 1 h followed by 24 h, 48 h, and 6 days in DBT free media produced effects on lytic function and ATP levels that were similar to those seen with continuous DBT exposures. The results indicate that DBT exposures decrease ATP levels in NK cells but that tumor lysing function can be reduced independent of any decreases in ATP levels. Additionally the results show that the effects of a range of DBT concentrations on ATP levels and tumor lysing function are irreversible.
Insights
Dibutyltin (DBT) exposure reduces natural killer (NK) cell tumor-lysing function, sometimes without decreasing ATP levels. These effects on NK cell function and ATP levels are irreversible, indicating DBT toxicity independent of energy depletion.
Area of Science:
- Immunology
- Toxicology
- Cell Biology
Background:
- Natural killer (NK) cells are crucial lymphocytes for identifying and eliminating tumor cells.
- Dibutyltin (DBT), a PVC stabilizer and poultry dewormer, is investigated for its impact on cellular functions.
- Understanding DBT's effects on NK cell lytic activity and cellular energy is vital for assessing its toxicological profile.
Purpose of the Study:
- To investigate the role of decreased adenosine triphosphate (ATP) levels in dibutyltin (DBT)-induced impairment of NK cell tumor-lysing function.
- To determine if DBT affects NK cell lytic function independently of changes in ATP levels.
- To assess the reversibility of DBT's effects on NK cell ATP levels and lytic function.
Main Methods:
- NK cells were exposed to various concentrations of DBT for different durations (1 hour to 6 days).
- ATP levels and tumor-cell-lysing (lytic) function were measured after DBT exposure.
- NK cells were also assessed after initial DBT exposure followed by incubation in DBT-free media to evaluate reversibility.
Main Results:
- Short-term DBT exposure (1 hour) significantly reduced NK cell lytic function without decreasing ATP levels.
- Longer exposures (48 hours, 6 days) to DBT caused significant decreases in both lytic function and ATP levels.
- DBT exposure impaired NK cell function and reduced ATP levels irreversibly, even after removal from DBT-containing media.
Conclusions:
- DBT exposure can decrease NK cell tumor-lysing function independently of significant reductions in cellular ATP levels.
- The observed effects of DBT on NK cell ATP levels and lytic function are irreversible.
- DBT exhibits toxicity towards NK cells that is not solely mediated by energy depletion.
