Cellular regulation of poly ADP-ribosylation of proteins: II. Augmentation of poly(ADP-ribose) polymerase in SV40 3T3 cells following methotrexate-induced G1/S inhibition of cell cycle progression

Journal Article · Fri May 01 00:00:00 EDT 1987 · Experimental Cell Research; (USA)

DOI:https://doi.org/10.1016/0014-4827(87)90119-4· OSTI ID:6531479

Sooki-Toth, A; Asghari, F; Kirsten, E; Kun, E ^[1]

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1. Univ. of California, San Francisco (USA)

SV40-3T3 cells were exposed in monolayer cultures to 5{times}10{sup {minus}7} M methotrexate (MTX), that inhibited thymidylate synthetase, arrested cell growth without cell killing in 24 h and did not induce single- (ss) or double-strand (ds) breaks in DNA. Following 24, up to 72 h, the poly(ADP-ribose) polymerase content of attached cells was induced by 5{times}10{sup {minus}7} MTX and the augmentation of the enzyme increased with the time of exposure to the drug. Inhibition of protein or RNA synthesis abolished augmentation of enzymatic activity; so too did the initiation of maximal cell growth by thymidine + hypoxanthine, by-passing the inhibitory site of MTX. Isolation of the ADP-ribosylated enzyme protein by gel electrophoresis identified poly(ADP-ribose) polymerase protein as the molecule that was induced by 5{times}10{sup {minus}7} M MTX. Under identical conditions, the poly(ADP-ribose) polymerase induction in 3T3 cells could not be demonstrated. A possible cell-cycle dependent biosynthesis of the enzyme protein is proposed in SV40 3T3 cells.

• OSTI ID: 6531479
• Journal Information: Experimental Cell Research; (USA), Vol. 170:1; ISSN 0014-4827
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
62 RADIOLOGY AND NUCLEAR MEDICINE
CELL CYCLE
MOLECULAR BIOLOGY
METHOTREXATE
BIOLOGICAL EFFECTS
POST-TRANSLATION MODIFICATION
BIOLOGICAL FUNCTIONS
RNA POLYMERASES
ENZYME INDUCTION
ELECTROPHORESIS
ENZYME INHIBITORS
FIBROBLASTS
METHIONINE
STRAND BREAKS
SULFUR 35
TRACER TECHNIQUES
TRITIUM COMPOUNDS
AMINO ACIDS
ANIMAL CELLS
ANTIMETABOLITES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
DRUGS
ENZYMES
EVEN-ODD NUCLEI
FUNCTIONS
GENE REGULATION
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIPOTROPIC FACTORS
NUCLEI
NUCLEOTIDYLTRANSFERASES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIOISOTOPES
SOMATIC CELLS
SULFUR ISOTOPES
TRANSFERASES
550201* - Biochemistry- Tracer Techniques
550301 - Cytology- Tracer Techniques
560300 - Chemicals Metabolism & Toxicology
550600 - Medicine