The effects of protaglandin E sub 2 and cyclooxygenase inhibition on ornithine decarboxylase activation and DNA synthesis during carbon tetrachloride-induced liver regeneration
Increases in prostaglandin E{sub 2} (PGE{sub 2}) and ornithine decarboxylase (ODC) activity are necessary for liver regeneration following surgical partial hepatectomy (SPH). The purpose of this study was to examine liver regeneration induced by carbon tetrachloride (CCl{sub 4}) to determine whether DNA synthesis initiation mechanisms involving PGE{sub 2} and ODC operated in a similar manner to that seen in SPH. The rat chemical partial hepatectomy (CPH) model was established in our laboratory as a method to examine regenerative processes. A characteristic time course of {sup 3}H thymidine incorporation into DNA was demonstrated which peaked 48 hours following CPH. Increases in liver specific serum sorbitol dehydrogenase (sSDH) and glutamate-pyruvate transaminase (sGPT) indicated that significant necrotic damage had occurred in the liver as a result of CCl{sub 4} toxicity. Increased DNA synthesis and necrotic damage in the liver satisfied criteria for use of this procedure as a model of regeneration. Hepatic PGE{sub 2} synthesis was measured using radioimmunoassay (RIA) during the 12 hr period following CPH. Increases in PGE{sub 2} concentration were seen at 2, 4, 6, and 8 hrs. Indomethacin (50 mg/kg) administered intraperitoneally 90 minutes prior to CPH inhibited increases in PGE{sub 2}. Therefore, increased PGE{sub 2} seen during this time is due to cyclooxygenase. Indomethacin administration did not inhibit DNA synthesis measured by {sup 3}H thymidine incorporation into DNA at 24, 48, 72, and 96 hrs. Thus the increased PGE{sub 2} concentrations seen in the period immediately following CPH are not required for DNA synthesis. Therefore, different mechanisms of DNA synthesis initiation are operative in CPH and SPH.
- Research Organization:
- Georgia Univ., Athens, GA (USA)
- OSTI ID:
- 5524437
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
CARBON TETRACHLORIDE
TOXICITY
DECARBOXYLASES
ENZYME ACTIVITY
LIVER
BIOLOGICAL REGENERATION
PROSTAGLANDINS
BIOCHEMICAL REACTION KINETICS
AMINOTRANSFERASES
CARBON 14 COMPOUNDS
DNA REPLICATION
ENZYME INHIBITORS
HEPATECTOMY
OXIDOREDUCTASES
RADIOIMMUNOASSAY
RATS
THYMIDINE
TRITIUM COMPOUNDS
ANIMALS
AZINES
BIOASSAY
BIOLOGICAL RECOVERY
BODY
CARBON-CARBON LYASES
CARBOXY-LYASES
CHLORINATED ALIPHATIC HYDROCARBONS
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
ENZYMES
GLANDS
HALOGENATED ALIPHATIC HYDROCARBONS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IMMUNOASSAY
IMMUNOLOGY
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEDICINE
NITROGEN TRANSFERASES
NUCLEIC ACID REPLICATION
NUCLEOSIDES
NUCLEOTIDES
ORGANIC CHLORINE COMPOUNDS
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RADIOASSAY
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
REACTION KINETICS
RECOVERY
RIBOSIDES
RODENTS
SURGERY
TRACER TECHNIQUES
TRANSFERASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques