CELL-CULTURES - A TOOL FOR THE STUDY OF MECHANISMS OF TOXICITY

Many toxic agents can affect cellular function by selectively interacting with cytoskeletal components, possible cell targets of toxicity. This phenomenon may represent the initial event in altering cell metabolism. The toxic effect of tributyltin chloride (TBT) on ATP levels, protein synthesis, glutathione (GSH) levels and lactate dehydrogenase (LDH) activity was investigated in a murine epidermal cell line (HEL-30). Recovery of cell functions was observed either when metabolism was induced by the addition to the incubation medium of an S-9 preparation, or when dithiothreitol (DTT) was added to the medium 5 min after the damage and in the absence of TBT. The level of F-actin, a cytoskeletal component, was lowered in resting human neutrophils by TBT and triphenyltin chloride (TPT) but not by SnCl2; moreover, the cellular response to a polymerizing stimulus such as fMLP, a chemotactic peptide, was no longer detectable after TBT or TPT treatment. The evidence that neutrophils of a subject who had been acutely exposed to TPT did not show the normal actin polymerization response to chemotactic stimulus (Colosio et al., British Journal of Industrial Medicine 1991, 48, 136) suggests a possible use of this function as a marker of human exposure to defined toxic chemicals.