The effects of Aroclor 1254 on undifferentiated and NGF-stimulated differentiating PC12 cells.
Rat pheochromocytoma [PC12] cells were used as models of a dopaminergic system to examine the effects of subchronic exposure to Aroclor 1254 on levels of cellular dopamine in undifferentiated and nerve growth factor (NGF)-stimulated differentiating cells. Either in the absence, or simultaneously in the presence of NGF, exposure to Aroclor 1254 resulted in dose-dependent decreases in levels of cellular dopamine, which with increasing time of exposure, up to 3 days, became increasingly sensitive to lower concentrations of PCBs as evidenced by shifts of the dose-response curves to the left. Pretreatment of PC12 cells with NGF for 7 or 14 days prior to exposure to Aroclor 1254 afforded partial protection from the PCB-mediated decreases in cellular dopamine, consistent with the hypothesis that the cells have different sensitivities to the dopamine decreasing effects of PCBs, depending on the state of differentiation that they are in when exposure to PCBs occurs. Exposure to Aroclor 1254 did not block the morphological aspects of NGF-induced neuronal differentiation, but rather enhanced the NGF-stimulated elongation of neurites in a dose-dependent manner. These results suggest that Aroclor 1254 reduces the levels of cellular dopamine, in both undifferentiated and differentiating PC12 cells, and that pretreatment with NGF may partially prevent PCB-mediated decreases in cellular dopamine. These results also suggest that Aroclor 1254 may enhance neurite elongation.
Angus
W G
WG
Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824, USA.
Contreras
M L
ML
D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D009414:Nerve Growth Factors; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats
D001140:Aroclors; D009414:Nerve Growth Factors; D004247:DNA; D004298:Dopamine