Prevention of tumorigenesis of oncogene-transformed rat fibroblasts with DNA site inhibitors of poly(ADP ribose) polymerase

Journal Article · Sun Feb 01 04:00:00 EST 1987 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.84.4.1107· OSTI ID:5934121

Tseng, A Jr; Lee, W M.F.; Kirsten, E; Hakam, A; McLick, J; Buki, K; Kun, E

The EJ-ras gene was placed under the transcriptional control of the steroid-inducible mouse mammary tumor virus promoter/enhancer and introduced into Rat-1 fibroblasts, yielding the 14C cell line. When these cells were exposed to dexamethasone in vitro, EJ-ras mRNA was induced 15- to 20-fold, the cells grew in agar, and, after injection of cells into syngenic Fischer 344 rats, they produced lethal fibrosarcomas. Inhibitors of poly(ADP ribose) polymerase, which prevent the activation of the purified enzyme by a synthrtic octadeoxyribonucleotide duplex, inhibited both in vivo tumorigenicity and in vitro growth in soft agar. The enzyme inhibitor 1,2-benzopyrone, which was studied in detail, and other polymerase inhibitors had no effect on EJ-ras mRNA or p21 protein expression. Poly(ADP ribose) polymerase was inhibited by the drug in both untreated and dexamethasone-treated cells both in vitro and in vivo to the same extent, but biological consequences of enzyme inhibition were manifest only when the cells were in the transformed tumorigenic state.

• Research Organization: Univ. of California, San Francisco
• OSTI ID: 5934121
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:4; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

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550300 -- Cytology
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CARCINOGENESIS
CELL TRANSFORMATIONS
CONNECTIVE TISSUE CELLS
CORTICOSTEROIDS
DAYS LIVING RADIOISOTOPES
DEXAMETHASONE
DNA
DNA POLYMERASES
ENZYME INHIBITORS
ENZYMES
FIBROBLASTS
GENES
GLUCOCORTICOIDS
HYBRIDIZATION
HYDROXY COMPOUNDS
INHIBITION
ISOTOPES
KETONES
KINETICS
LIGHT NUCLEI
MAMMALS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDYLTRANSFERASES
ODD-ODD NUCLEI
ONCOGENES
ONCOGENIC TRANSFORMATIONS
ORGANIC COMPOUNDS
PATHOGENESIS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PREGNANES
RADIOISOTOPES
RATS
REACTION KINETICS
RODENTS
SOMATIC CELLS
STEROIDS
TRANSFERASES
VERTEBRATES