Brief butyltin exposure induces irreversible inhibition of the cytotoxic function on human natural killer cells, in vitro

Despite mounting evidence on butyltin (BT) contamination and related immunotoxic effects on wildlife, very little is known about BT-associated immunotoxic effects on humans, particularly the effects on human natural killer (NK) lymphocyte function. Our earlier studies demonstrated that in vitro exposure to environmentally relevant concentrations of BTs negatively affect human NK cells and that there are measurable levels of BTs in human blood. In this study we examined whether the inhibition of NK cell cytotoxic function induced by a brief exposure (1 h) to BTs is reversible when the cells are allowed to recover in BT-free media for up to 6 days. Standard methods were used in chemical preparation, blood sampling, NK cell isolation, and 51-Chromium release assay. The results revealed that exposure to 300 nM TBT for 1 h caused an approximately 65- decrease in NK cytotoxic function, whether the lymphocytes were given as long as a 6-day recovery period or no recovery period. There was no recovery (nor any further loss) of NK cytotoxic function following removal of the compound. Exposure to 5 microM DBT for 1 h showed a 41% decrease in cytotoxic function with 0-h recovery and an 83% decrease after a 24-h recovery period. Thus, not only is there no significant recovery of NK cytotoxic function when the lymphocytes are allowed to incubate in BT-free medium for up to 6 days but there is additional loss of cytotoxic function. The results indicated that short-term exposure to BTs causes persistent negative effects on NK cell ability to kill cancer cells.