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INCREASED [3H]-PHORBOL ESTER BINDING IN RAT CEREBELLAR GRANULE CELLS BY POLYCHLORINATED BIPHENYL MIXTURES AND CONGENERS: STRUCTURE-ACTIVITY RELATIONSHIPS
Citation:
Kodavanti, P., T. Ward, J. McKinney, AND H. Tilson. INCREASED [3H]-PHORBOL ESTER BINDING IN RAT CEREBELLAR GRANULE CELLS BY POLYCHLORINATED BIPHENYL MIXTURES AND CONGENERS: STRUCTURE-ACTIVITY RELATIONSHIPS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/153.
Description:
Our previous reports indicate that the neuroactivity of polychlorinated biphenyl (PCB) congeners may be associated with perturbations in cellular Ca2-homeostasis, and protein kinase C (PKC) activation/translocation. e have now studied the structure-activity relationship of several PCB mixtures and congeners for their effects on PKC activation/translocation by measuring [3H]- phorbol ester ([3H]-PDBu) binding in cerebellar granule cells (7 days in culture). f the mixtures studied, Aroclor 1016 and Aroclor 1254 were more potent when compared to Aroclor 1260. f the twenty four congeners studied, diortho-congeners like 2,2',5,5'-tetrachlorobiphenyl, 2,2',4,6,6'pentachlorobiphenyl, 2,2',4,6'-tetrachlorobiphenyl, and 2,2',5,5'-pentachlorobiphenyl were not affective. he potential contaminant of PCB mixtures, 1,2,3,7,9-pentachlorodibenzofuran has no effect on [3H]-PDBu binding. he structure-activity relationships among these congeners revealed: (1) congeners with ortho- or ortho-lateral (meta, para) chlorine substitutions were most potential(2) congeners with only para substitution or high lateral content in the absence of ortho-substitution were not effective (3) increased chlorination was not clearly related to the effectiveness of these congeners, although hexa- and hepta-chlorination is less effective when compared to di- and tetra-chlorination. ow lateral substitution, especially without para substitution, or lateral content in the presence of ortho substitution, may be the most important structural requirement for the neuroactivity of these PCB congeners.