The purpose of this study was to investigate the role that
tributyltin (TBT)-induced decreases in
ATP levels may play in TBT-induced decreases in the
tumor lysing (lytic) function of natural killer (NK) cells. NK cells are a subset of lymphocytes that act as an initial immune defense against
tumor cells and virally infected cells. TBT is an environmental contaminant that has been detected in human blood, which has been shown to interfere with
ATP synthesis. Previous studies have shown that TBT is able to decrease very significantly the lytic function of NK cells. In this study NK cells were exposed to various concentrations of TBT and to two other compounds that interfere with
ATP synthesis (
rotenone a complex I inhibitor and
oligomycin an
ATP synthase inhibitor) for various lengths of time before determining the levels of
ATP and lytic function. Exposures of NK cells to 10, 25, 50 and 100 nm TBT did not significantly reduce
ATP levels after 24 h. However, these same exposures caused significant decreases in cytotoxic function. Studies of brief 1 h exposures to a range of TBT,
rotenone and
oligomycin concentrations followed by 24 h, 48 h and 6 day periods in compound-free media prior to assaying for
ATP levels or cytotoxic function showed that each of the compounds caused persistent decreases in
ATP levels and lytic function of NK cells. Exposures to 0.05-5 microm
rotenone or
oligomycin for 1 h reduced
ATP levels by 20-25% but did not have any measurable effect on the ability of NK cells to lyse
tumor cells.
ATP levels were also decreased by about 20-25% after 24 h or 48 h exposures to
rotenone or
oligomycin (0.5 microm ), and the lytic function was decreased by about 50%. The results suggest that TBT-induced decreases in
ATP levels were not responsible for the loss of cytotoxic function seen at 1 h and 24 h. However, TBT-induced decreases of NK-
ATP levels may be at least in part responsible for losses of NK-cytotoxic function seen after 48 h and 6 day exposures.