Two polychlorinated hydrocarbons cause phospholipid-dependent protein kinase C activation in vitro in the absence of calcium.
Polychlorinated hydrocarbons known to be nongenotoxic carcinogens were screened as activators of protein kinase C (PKC)-beta 1 either at high concentrations of Ca2+ or in the absence of Ca2+ (i.e., with 1 mM ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N',-tetraacetic acid). Of those compounds tested, kepone and dicofol significantly stimulated PKC activity in the absence, but not the presence, of Ca2+. PKC activation was most pronounced in the presence of phosphatidylserine. Kepone and dicofol stimulated PKC activity 26% and 13%, respectively, as compared with the PKC activity (100%) stimulated by the tumor-promoting phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). Northern blot analysis of expression of TPA-inducible genes by kepone showed slight expression of phorbin and ornithine decarboxylase in murine embryo fibroblasts. Future studies are required to determine the relevance of PKC activation by kepone and dicofol to the known carcinogenicity of these compounds.
Rotenberg
S A
SA
Institute of Cancer Research, Columbia University, New York, NY 10032.
Weinstein
I B
IB
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D007631:Chlordecone / Q000494:pharmacology*; D004010:Dicofol / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D009955:Ornithine Decarboxylase / Q000235:genetics; D010718:Phosphatidylserines / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases
D006023:Glycoproteins; D010718:Phosphatidylserines; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D007631:Chlordecone; D002118:Calcium; D004010:Dicofol