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PCB-INDUCED CHANGES IN THE DNA BINDING OF SEVERAL TRANSCRIPTION FACTORS IN THE DEVELOPING CEREBELLUM.
Citation:
Basha, M. R., N. S. Bandy, PRS Kodavanti, AND N. H. Zawia. PCB-INDUCED CHANGES IN THE DNA BINDING OF SEVERAL TRANSCRIPTION FACTORS IN THE DEVELOPING CEREBELLUM. Presented at Society of Toxicology, Nashville, NC, March 17-21, 2002.
Description:
Polychlorinated biphenyls (PCBs) are a class of persistent chemical pollutants prevalent in the environment despite the ban of their use for decades. Disturbances in brain development and cognition are among the neurotoxic manifestations of PCBs. The cellular and molecular basis for PCB-induced developmental neurotoxicity is still unclear, however, a series of in vitro and some in vivo studies have revealed that the disruption of Ca2+ homeostasis and Ca2+ mediated signal transduction play a significant role. The culminating event in a variety of signal transduction pathways is the regulation of gene expression. Therefore, we examined the DNA-binding of several transcription factors in order to identify those that are involved in signal transduction/transcription coupling in the developing brains of PCB-exposed animals. Pregnant rats (Long Evans) were exposed perinatally to 0 or 6 mg/kg/day of Aroclor 1254 (AccuStandard Inc., Lot # 124-191) from gestation day 6 through postnatal day (PND) 21. On specific PNDs viz., 7, 14, 21, and 60, the cerebellum was isolated. The DNA-binding of various transcription factors: Sp1, AP1, NF-kB and CREB was then monitored using gel mobility shift assays. While an overall transient increase in the DNA-binding of all the transcription factors was observed following birth, this period was characterized by a pronounced induction in Sp1 and NF-kB DNA-binding. The distinct changes in Sp1 and NF-kB DNA-binding suggest that they may be involved in mediating PCB-induced perturbations in gene expression that occur during perinatal brain development. (The abstract does not necessarily reflect USEPA policy).