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.

The purpose of this study is to investigate the relationship between ATP levels in human natural killer (NK) cells and their cytotoxic function. NK cells are a subset of lymphocytes that act as primary defense against tumor cells and virally infected cells. NK cells were exposed to various concentrations of rotenone (RO), oligomycin (OL), and tributyltin (TBT) for various lengths of time before determining the levels of ATP (using a chemiluminescent assay) and cytotoxic function (determined by a chromium release assay). RO inhibits ATP production at Complex I, while OL inhibits ATP synthase. TBT is an environmental contaminant and has been detected in human blood. A 1 h exposure to either 0.5 μM RO or OL reduced ATP levels by about 20% but did not have any measurable effect on cytotoxic function. Both 24 h and 48 h exposures to these compounds caused a 20–25% reduction in ATP levels. Cytotoxic function was reduced by about 50% after 24 h or 48 h exposures to 0.5 μM RO. A 24 h exposure to 0.5 μM OL reduced cytotoxic function by about 50%, while a 48 h exposure reduced it by about 75%. It was observed that concentrations of 10, 25, 50, and 100 nM TBT did not significantly reduce ATP levels after 24 h, however they caused significant decreases in cytotoxic function. Cell viability was not affected by exposure to these compounds as determined by trypan blue exclusion. The results of this study indicate that decreased ATP levels may lead to decreased NK cytotoxic function but there is no absolute association. They also indicate that TBT‐induced decreases in NK cytotoxic function cannot be attributed to TBT‐induced decreases in ATP levels alone. Supported by NIH grant 2S06GM08092‐28