Cytotoxic effects in mammalian Vero cells exposed to pentachlorophenol

The effects of pentachlorophenol have been studied on diverse biological systems both in vivo and in vitro, however the cellular basis of the pronounced cytotoxicity of this organochlorine compound is poorly understood. In this work, morphological and biochemical analyses were carried out to identify the primary targets of pentachlorophenol toxicity in mammalian cells. Our results show that pentachlorophenol is a very potent cytotoxic drug that displays an unusual and interesting mode of action in Vero cells. Although this compound is a powerful uncoupler of oxidative phosphorylation, we present the novel finding that lysosome destabilization is an early cytotoxic response that precedes the mitochondrial dysfunction. In addition, soon after exposure to moderate doses of pentachlorophenol, a significant number of cells initiate an apoptotic death process identified by the condensed and fragmented state of their nuclei. These results demonstrate that there are multiple potential targets of PCP-induced toxicity in mammalian cells, and the need to develop further experimental studies for the risk assessment of this environmental pollutant. (c) 2005 Elsevier Ireland Ltd. All rights reserved.