Activation of the EBV-cycle and aggregation of human blood lymphocytes by the tumor promoters teleocidin, lyngbyatoxin A, aplysiatoxin and debromoaplysiatoxin.
A variety of tumor promoters such as the phorbol esters were found to be capable of inducing the viral cycle in cell lines latently infected with Epstein-Barr virus (EBV). We tested two classes of new tumor promoters; indole alkaloids and polyacetates, for their ability to induce the synthesis of the Epstein-Barr virus determined early antigen (EA) complex. Teleocidin and lyngbyatoxin A are indole alkaloids. Aplysiatoxin and debromoaplysiatoxin are polyacetates. Of these four tumor promoters all but debromoaplysiatoxin induced the synthesis of the EA complex. However, in combination with 3 mM n-butyrate, all four induced EA synthesis. The potent tumor promoters teleocidin, lyngbyatoxin A and aplysiatoxin induced maximal synthesis of EA at the concentration of 5 to 10 ng/ml, whereas the weak tumor promoter debromoaplysiatoxin required a concentration of 250 ng/ml to achieve maximal induction. Phorbol esters induce quick morphological changes and aggregation of human blood lymphocytes. The latter phenomenon has been interpreted as the expression of a "cell binding phenotype" (Patarroyo et al., in press). We showed that all four promoters induced aggregation of human lymphocytes at similar concentrations. The induction seemed to be a common effect which could be induced by both strong and weak tumor promoters.
D000470:Alkaloids / Q000494:pharmacology*; D000956:Antigens, Viral; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; D002449:Cell Aggregation / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D066298:In Vitro Techniques; D007783:Lactones / Q000494:pharmacology*; D008214:Lymphocytes / Q000187:drug effects*; D008235:Lyngbya Toxins; D008387:Marine Toxins / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C; D011956:Receptors, Cell Surface / Q000187:drug effects; D011955:Receptors, Drug; D014775:Virus Activation / Q000187:drug effects
D000470:Alkaloids; D000956:Antigens, Viral; D029742:Caenorhabditis elegans Proteins; D002273:Carcinogens; D002352:Carrier Proteins; C033305:Epstein-Barr virus early antigen; D007783:Lactones; D008235:Lyngbya Toxins; D008387:Marine Toxins; D010703:Phorbol Esters; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; C083141:phorbol ester binding protein; C027776:phorbol ester receptor; C022176:teleocidins; C017179:debromoaplysiatoxin; C006610:aplysiatoxin; D011493:Protein Kinase C; C019457:lyngbyatoxin A