Suppression of Dexamethasone-Stimulated DNA Synthesis in an Oncogene ConstructContaining Rat Cell Line by a DNA Site-Oriented Ligand of Poly-ADP-Ribose Polymerase: 6-Amino-1,2-Benzopyrone

摘要

The cellular inhibitory effects of 6-amino-1,2-benzo-pyrone (6-ABP), a DNA site-specific ligand of adenosine diphosphoribisoyl transferase (ADPRT), were determined in a dexamethasone-sensitive EJ-ras gene construct containing cell line (14C cells). Dexamethasone in vitro transforms these cells to a tumorigenic phenotype and also stimulates cell replication. At a nontoxic concentration (0.2 mM) 6-ABP treatment of intact cells for 4 days inhibits the dexamethasone stimulated increment of cellular DNA content, depresses replicative DNA synthesis as assayed by thymidine incorporation to the level of cells that were not exposed to dexamethasone, and in permeabilized cells reduces the dexamethasone-stimulated increase of deoxyribonucleotide incorporation into DNA to the level of untreated cells.