Effects of butyltin exposures on the transcription regulator AP-1.

摘要

Natural killer (NK) cells are a specific type of lymphocytes known for their ability to lyse tumor cells, virally infected cells, and antibody coated cells. Butyltins (BT) are organotin compounds that have an enormous industrial application. Tributyltin (TBT) has widely known uses as a marine antifoulant and wood preservative. Dibutyltin (DBT) is used as a stabilizer in plastic products such as polyvinyl chloride (PVC) pipes and food storage bags. TBT has been detected in fish and DBT has been discovered in beverages contained in PVC pipes during the manufacturing process. The aim of this study was to test whether the effects of exposures to BTs can alter the activation states as well as the levels of the immediate early genes c-jun, c-fos (Activating Protein-1, AP-1) and the mitogen-activated protein kinase (MAPK)-responsive transcription factor elk-1. AP-1 is a transcription factor complex, formed by dimerization of members from the jun and fos gene family. It is hypothesized that exposures to these compounds may alter the levels and/or function of MAPK dependent transcription regulators (e.g. AP-1). NK cells exposed to 300nM TBT for 10 minutes showed a significant increase the phosphorylation of the protein c-jun. A 1 hour exposure to 300 nM and 200 nM TBT caused significant increases in the phosphorylation of c-jun and the levels of c-jun. When NK cells were exposed to 100 and 25 nM TBT for 1 hour, a significant increase in the total level of the protein c-fos resulted. During a 300 nM treatment with TBT for 1 hour the binding activity of c-fos was significantly decreased by 18%. Treatments with TBT or DBT for 6 hours showed no significant changes. Thus, the data suggest that TBT-induced alterations on phosphorylation, total levels and binding activity of c-fos or c-jun might contribute to, but are not fully responsible for, TBT-induced alteration of the transcription factor AP-1.