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COMPARATIVE EFFECTS OF TWO POLYCHLORINATED BIPHENYL CONGENERS ON CALCIUM HOMEOSTASIS IN RAT CEREBELLAR GRANULE CELLS
Citation:
Kodavanti, P., D. Shin, H. Tilson, AND G. Harry. COMPARATIVE EFFECTS OF TWO POLYCHLORINATED BIPHENYL CONGENERS ON CALCIUM HOMEOSTASIS IN RAT CEREBELLAR GRANULE CELLS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-94/072.
Description:
Some polychlorinated biphenyls (PCBs) have been reported to alter locomotor activity and decrease brain dopamine function in laboratory animals. CBs with orth- and/or para-chlorine substitutions are reportedly most potent in decreasing cell dopamine content in vitro and were detected in brains of animals exposed to PCBs suggesting that the neurotoxicity could be mediated by ortho-substituted congeners. opamine or other neurotransmitter uptake and release phenomena are dependent on the maintenance of intracellular Ca2+ -homeostasis, and perturbations in CA2+ altered cell function and/or death. e compared the effects of two PCB congeners, with different chlorine substitutions, on Ca2+ -homeostasis in cerebellar granule cells: 2,2'-Dichlorobiphenyl (DCBP), a putative neurotoxic congener and 3,3',4,4'5-pentachlorobiphenyl (PCBP), a putative neurotoxic congener. n cerebellar granule cells (6-8 days in vitro), DCBP was cytotoxic as indicated by a significant increase in LDH leakage at 200 uM after 2 hr of exposure, and at 100uM after 4 hr exposure. CBP, on the other hand, did not affect LDH leakage even at 200 uM for up to 4 hr. lthough both congeners increased cerebellar granule cell [Ca2+], DCPB was more effective in increasing [Ca2+] to a greater extent than PCBP. he increase in [Ca2+], produced by both congeners was not transient, but a steady rise was observed with time. CBP was a potent inhibitor of 45Ca2+ -sequestration by mitochondria (1C50=6.17+0.53uM) and microsomes (iC50=7.61=0.35uM).