Evaluation of TBT toxicity on murine macrophages and their intracellular targets

Triorganotins, because of their wide application as heat stabilizers for PVC polymers, biocides, and catalysts, have been extensively used in recent years and there is a great concern about their toxicity in the environment. A primary target for tributyltin (TBT) toxicity, at least in rodents, is the immune system, with thymic atrophy serving as a hallmark feature of exposure. Moreover, it is known that TBT is able to induce both cytoskeletal alterations and apoptosis in mammalian thymocytes. In order to explain the molecular mechanism which is responsible for the effcts observed in whole organisms, in this study we have evaluated the effects of TBT in cultures of murine peritoneal macrophages. After 24 h exposure at increasing doses of TBT, the MTT test showed a dose-dependent cytotoxicity with an IC50 value of about 3 \ub5M. Since the inhibition of mitochondrial activity by TBT is well known, our investigations were focused on lysosomes prepared from the same murine peritoneal macrophages in which the toxicity has been evaluated. By means of a probe for the measurement of internal pH by acridine orange, it was observed that TBT inhibits the lysosomal acidification. A possible explanation of these results is that TBT behaves as uncoupler in both mitochondria and lysosomes