Induction of rat liver O6-alkylguanine-DNA alkyltransferase following whole body X-irradiation
The promutagenic DNA lesion O6-alkylguanine can be enzymically removed from cellular DNA by an O6-alkylguanine-DNA alkyltransferase (O6-AT) which transfers the alkyl group from the O6-position of guanine to a cysteine residue contained within its sequence. We report that whole body X-irradiation induces the O6-AT activity in the liver of adult Wistar rats. In vivo repair activity was assessed by radiochromatographic determination of the persistence of O6-methylguanine in hepatic DNA of irradiated rats following a single i.p. injection of N-nitroso-(/sup 14/C)dimethylamine (2 mg/kg). In addition, the O6-alkylguanine repair capacity was assayed in vitro by incubation of extracts from whole liver, hepatocytes, or hepatic cell nuclei with /sup 3/H-methylated DNA and high performance liquid chromatography analysis of this DNA substrate. We found that whole body X-irradiation increased in a dose-dependent manner the O6-AT activity over a range of 100-800 R. The repair induction was first detectable 12 h after X-ray exposure, reached a maximum level at 72 h, and declined to control values within 12 days. Deoxythymidine incorporation into hepatic DNA was significantly reduced during the initial 72 h following application of 500 R. In a split dose irradiation schedule with daily doses of 15 R, a delayed enzyme induction occurred after a 30-day treatment period. Pretreatment of rats with the translational inhibitor cycloheximide completely suppressed the O6-AT stimulation. This indicates that the induction of hepatic O6-alkylguanine repair is due to de novo synthesis of alkyltransferase molecules.
- OSTI ID:
- 5632962
- Journal Information:
- Cancer Res.; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
LIVER
BIOLOGICAL RADIATION EFFECTS
TRANSFERASES
ENZYME INDUCTION
BIOCHEMICAL REACTION KINETICS
CARBON 14 COMPOUNDS
CELL NUCLEI
CYCLOHEXIMIDE
DNA
DNA REPAIR
DOSE-RESPONSE RELATIONSHIPS
GUANINE
LIQUID COLUMN CHROMATOGRAPHY
NITROSAMINES
RATS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
WHOLE-BODY IRRADIATION
AMINES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CELL CONSTITUENTS
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DRUGS
ENZYMES
EXTERNAL IRRADIATION
FUNGICIDES
GENE REGULATION
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IRRADIATION
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
MAMMALS
NITROSO COMPOUNDS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PESTICIDES
PURINES
RADIATION EFFECTS
REACTION KINETICS
RECOVERY
REPAIR
RODENTS
SEPARATION PROCESSES
VERTEBRATES
560152* - Radiation Effects on Animals- Animals