The effects of tributyltin on the transcription regulator AP‐1

Abstract

Tributyltin (TBT) is a widespread environmental contaminant and there is significant exposure of humans to TBT. Measurable levels of TBT have been found in human blood samples. It appears to increase the risk of cancer and viral infections in exposed individuals. Natural Killer (NK) cells are lymphocytes that are capable of killing tumor cells, virally infected cells and antibody coated cells. NK cells are our primary immune defense against viruses and cancer cells. In past studies, we demonstrated that exposure to TBT produced a decrease in the tumor‐cell killing function of human NK cells. Previous studies also showed that exposure of NK cells to TBT activated mitogen activated protein kinases (MAPKs), p44/42 and p38. MAPKs are known to be critical regulators of the tumor‐destroying function of NK cells, in part, by their capacity to alter the function of the transcription regulator AP‐1. The current study addresses the effect of TBT exposure on the phosphorylation state and overall levels of the AP‐1 components, Fos and jun. Such studies are necessary to determine if the alterations in MAPK activity induced by TBT are potentially altering the function of these transcription regulators. NK cells were exposed to TBT and the levels and/or phosphorylation states of Fos and jun were determined using western blotting. The results showed that there was an increase in the phosphorylation (activation) of jun within 10 min of exposure to TBT. There was also an increase in the overall level of fos within 1 hour exposure to the compound. The results indicated that there were alterations of the components of AP‐1, which would result in increased functional capacity. Altered AP‐1 function could in part explain changes in the expression of several NK proteins that have previously been observed.