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Title: Studies on the induction of Epstein-Barr virus (EBV) DNA polymerase (POL) and deoxyribonuclease (DNase) by the combined action of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and N-butyrate (SB in EBV-carrying cells

Abstract

TPA and SB were found to induce EBV early antigen in EBV-carrying Raji cells, a Burkitt's Lymphoma-derived human cell line. The mode of interaction of these agents was unclear. They have examined the induction of EBV-POL and DNase activities by TPA and SB. It was found that neither agent alone could induce EBV-POL and DNase activities, even though the virus DNA could be induced by either compound alone. Induction of virus enzymes could only occur when cells were exposed to both compounds. A 2h exposure to TPA followed by 46h to SB resulted in levels of induction of EBV-POL and DNase activities comparable to those induced with simultaneous exposure to both agents for 48h. No induction of the enzymes will occur if the sequence of exposure to these agents is reversed. Phospholipase C, which increases intracellular diacylglycerol (and subsequently the activation of Protein Kinase C), and 5-Aza-deoxycytidine, a DNA hypomethylating agent, were able to partially substitute for TPA and SB, respectively. These results suggest that the mechanism of induction of EBV enzyme activities by TPA and SB could involve both Protein Kinase C activation and DNA hypomethylation. Furthermore, the synthesis of EBV DNA is not sufficient for induction of thesemore » virus enzyme activities.« less

Authors:
; ; ; ;
Publication Date:
Research Org.:
Univ. of North Carolina, Chapel Hill
OSTI Identifier:
7132292
Report Number(s):
CONF-8604222-
Journal ID: CODEN: FEPRA
Resource Type:
Conference
Resource Relation:
Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States); Journal Volume: 45:4; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; BUTYRIC ACID; BIOLOGICAL EFFECTS; DNA POLYMERASES; ENZYME INDUCTION; DNA-ASE; PHORBOL ESTERS; DNA REPLICATION; ENZYME ACTIVITY; PHOSPHOTRANSFERASES; VIRUSES; CARBOXYLIC ACIDS; CARCINOGENS; ENZYMES; ESTERASES; ESTERS; GENE REGULATION; HYDROLASES; MICROORGANISMS; MONOCARBOXYLIC ACIDS; NUCLEIC ACID REPLICATION; NUCLEOTIDYLTRANSFERASES; ORGANIC ACIDS; ORGANIC COMPOUNDS; PARASITES; PHOSPHODIESTERASES; PHOSPHORUS-GROUP TRANSFERASES; POLYMERASES; TRANSFERASES 560300* -- Chemicals Metabolism & Toxicology

Citation Formats

Nutter, L.M., Tan, R.S., Grill, S., Li, J.S., and Cheng, Y.C. Studies on the induction of Epstein-Barr virus (EBV) DNA polymerase (POL) and deoxyribonuclease (DNase) by the combined action of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and N-butyrate (SB in EBV-carrying cells. United States: N. p., 1986. Web.
Nutter, L.M., Tan, R.S., Grill, S., Li, J.S., & Cheng, Y.C. Studies on the induction of Epstein-Barr virus (EBV) DNA polymerase (POL) and deoxyribonuclease (DNase) by the combined action of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and N-butyrate (SB in EBV-carrying cells. United States.
Nutter, L.M., Tan, R.S., Grill, S., Li, J.S., and Cheng, Y.C. 1986. "Studies on the induction of Epstein-Barr virus (EBV) DNA polymerase (POL) and deoxyribonuclease (DNase) by the combined action of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and N-butyrate (SB in EBV-carrying cells". United States. doi:.
@article{osti_7132292,
title = {Studies on the induction of Epstein-Barr virus (EBV) DNA polymerase (POL) and deoxyribonuclease (DNase) by the combined action of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and N-butyrate (SB in EBV-carrying cells},
author = {Nutter, L.M. and Tan, R.S. and Grill, S. and Li, J.S. and Cheng, Y.C.},
abstractNote = {TPA and SB were found to induce EBV early antigen in EBV-carrying Raji cells, a Burkitt's Lymphoma-derived human cell line. The mode of interaction of these agents was unclear. They have examined the induction of EBV-POL and DNase activities by TPA and SB. It was found that neither agent alone could induce EBV-POL and DNase activities, even though the virus DNA could be induced by either compound alone. Induction of virus enzymes could only occur when cells were exposed to both compounds. A 2h exposure to TPA followed by 46h to SB resulted in levels of induction of EBV-POL and DNase activities comparable to those induced with simultaneous exposure to both agents for 48h. No induction of the enzymes will occur if the sequence of exposure to these agents is reversed. Phospholipase C, which increases intracellular diacylglycerol (and subsequently the activation of Protein Kinase C), and 5-Aza-deoxycytidine, a DNA hypomethylating agent, were able to partially substitute for TPA and SB, respectively. These results suggest that the mechanism of induction of EBV enzyme activities by TPA and SB could involve both Protein Kinase C activation and DNA hypomethylation. Furthermore, the synthesis of EBV DNA is not sufficient for induction of these virus enzyme activities.},
doi = {},
journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:4,
place = {United States},
year = 1986,
month = 3
}

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  • 12-O-Tetradecanoyl-phorbol-13-acetate (TPA) in conditions that produce enhancement of ultraviolet light (UV) and x-irradiation Syrian hamster embryo cell (HEC) transformation did not cause further increase in the sister chromatid exchange (SCE) frequency induced by UV and x-irradiation, two physical carcinogens that differ in their mode of DNA interaction and efficiency of SCE induction. Several factors which might influence SCE induction by TPA were studied on HEC and Chinese hamster V79-4 cells. Heat-inactivated serum was used because of the possibility that a serum component may interfere with TPA ability to cause SCE. TPA effect on SCE was determined at the first andmore » second division post treatment on cells exposed to different 5-bromodeoxyuridine (BrdUrd) concentrations. Independent of BrdUrd concentration (1-10..mu..g/ml medium) and the number of cells divisions post treatment, TPA (0.01-2..mu..g/ml medium) was ineffective in inducing SCE in exponentially and stationary HEC cultures cultivated in medium supplemented with heat-inactivated serum. Also, TPA did not increase the SCE frequency in V79-4 Chinese hamster cells cultured in heat-activated or noninactivated serum. Although SCE induction, a cellular response to carcinogen-induced DNA damage, may be important for the induction of transformation by environmental agents, the enhancement of transformation frequency caused by TPA occurs without further DNA alterations involved in SCE formation.« less
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