Apoptosis-mediated neurotoxic potential of a planar (PCB 77) and a nonplanar (PCB 153) polychlorinated biphenyl congeners in neuronal cell cultures.
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants, some of which may be neurotoxic depending on the chemical structure of the congeners. This study investigated the neurotoxic potential of 3,3',4,4'-tetrachlorobiphenyl (TCB) (PCB 77, a non-ortho-substituted planar congener) and 2,2',4,4',5,5'-hexachlorobiphenyl (HCB) (PCB 153, a di-ortho-substituted nonplanar congener) by assessing cell viability and apoptotic cell death in neuronal cell cultures. We have combined morphological and biochemical techniques to establish the relevance of apoptosis in neuronal cell death induced by the two selected PCB congeners. Treatment with both planar and nonplanar congeners caused the loss of cell viability and accelerated apoptosis in a time- and concentration-dependent manner. However, the extent of apoptosis generated was greater for the non-ortho-substituted planar congener (PCB 77) than for the di-ortho-substituted nonplanar congener (PCB 153). This was correlated with the loss of cell viability since the planar congener was more cytotoxic. Based on our findings, the apoptosis induced by PCBs involves the increase of caspase-3 activity in neuronal cell cultures. It is reasonable to assume that PCB-induced apoptosis may be linked to the neurotoxic effect of these toxicants and that different molecular mechanisms may operate in the induction of apoptosis depending on the planarity or nonplanarity of the PCB congeners.
Sánchez-Alonso
Jesús Adolfo
JA
Departamento de Bioquímica y Biología Molecular, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.
López-Aparicio
Pilar
P
Recio
María N
MN
Pérez-Albarsanz
Miguel A
MA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000494:pharmacology; D018929:Cell Culture Techniques; D002470:Cell Survival; D002540:Cerebral Cortex; D004785:Environmental Pollutants / Q000633:toxicity*; D009474:Neurons / Q000473:pathology*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C028451:3,4,3',4'-tetrachlorobiphenyl; C014024:2,4,5,2',4',5'-hexachlorobiphenyl