Induction of apoptotic cell death by a p53-independent pathway in neuronalSK-N-MC cells after treatment with 2,2 ',5,5 '-tetrachlorobiphenyl

Apoptotic cell death is an active process, which is a critical feature of t he regulated development of multicellular organisms. Polychlorinated biphen yls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic. This study investigates the 2,2', 5,5'-tetrachlorobiphenyl (PCB 52) induced apoptosis in human neuronal SK-N-MC cells, and the role of p53 in this response. Upon treatments with PCB 52, time- and concentration-dep endent inhibition of the cell viability was observed. PCB 52 also caused ap optosis, as measured by cell morphology and DNA fragmentation. The capabili ty of PCB 52 to induce apoptosis was associated with the proteolytic cleava ge of specific target proteins, such as poly(ADP-ribose) polymerase (PARP) and beta -catenin proteins, suggesting the possible involvement of caspases . In general, DNA-damaging agents induce accumulation of the tumor suppress or protein p53, leading cells to either growth arrest in G1, or apoptosis. However, our data showed that both p53 and Bcl-2 protein levels were decrea sed in a time-dependent manner during apoptosis after exposure to PCB 52. T hese results suggest that PCB 52 induced a p53-independent apoptosis in the se cells. (C) 2001 Published by Elsevier Science Ireland Ltd. All rights re served.