Carcinogen-inflicted DNA damage causes a dramatic increase in the degradation of chromatin-bound poly(ADP-ribose) in mammalian cells

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6176619

Alvarez-Gonzalez, R; Althaus, F R

A characteristic response of eukaryotic cells to treatment with carcinogens is de novo poly(ADP-ribosylation) of chromatin proteins, a reaction which acts to modulate subsequent DNA excision repair by a hitherto unidentified molecular mechanism. DNA strand breaks represent the molecular signal which activates the chromatin enzyme poly(ADP-ribose) polymerase and thus stimulates poly(ADP-ribose) biosynthesis. They have now observed that carcinogen-inflicted DNA damage may also cause a more than 600-fold stimulation of the degradation of protein-bound poly(ADP-ribose) in chromatin of rat hepatocytes in primary culture. As a consequence, the metabolic half-life of the polymer decreases from 7.7 h in undamaged control cells to 5.5 min and 2.5 min following damage of cells with 45 and 150 J/m/sup 2/ of UV light of 254 nm, respectively. Similarly, damage of hepatocellular DNA inflicted with either 20, 50 or 200 ..mu..M N-methyl-N'-nitro-N-nitrosoguanidine, a monofunctional alkylating agent, caused a dramatic decrease in the polymer half-life to 5.1 min, 2.3 min, and 41 sec, respectively. Therefore, their results suggest that the dynamic removal of polymeric ADP-ribose residues from their chromatin acceptors represents an obligatory postincisional event in DNA excision repair of mammalian cells.

• Research Organization: Noble Foundation, Inc., Ardmore, OK
• OSTI ID: 6176619
• Report Number(s): CONF-870644-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
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& Tissue Culture
560300 -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADP
ALDEHYDES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
CARBOHYDRATES
CARCINOGENESIS
DNA
DNA POLYMERASES
DNA REPAIR
ELECTROMAGNETIC RADIATION
ENZYMES
GENETIC EFFECTS
GENETIC RADIATION EFFECTS
LIVER CELLS
MAMMALS
METABOLISM
MONOSACCHARIDES
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PENTOSES
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
RADIATION EFFECTS
RADIATIONS
RATS
RECOVERY
REPAIR
RIBOSE
RODENTS
SACCHARIDES
SOMATIC CELLS
STRAND BREAKS
TRANSFERASES
ULTRAVIOLET RADIATION
VERTEBRATES