Persistent and heritable structural damage induced in heterochromatic DNA from rat liver by N-nitrosodimethylamine
Analysis, by benzoylated DEAE-cellulose chromatography, has been made of structural change in eu- and heterochromatic DNA from rat liver following administration of the carcinogen N-nitrosodimethylamine. Either hepatic DNA was prelabeled with (/sup 3/H)thymidine administered 2-3 weeks before injection of the carcinogen or the labeled precursor was given during regenerative hyperplasia in rats treated earlier with N-nitrosodimethylamine. Following phenol extraction of either whole liver homogenate or nuclease-fractionated eu- and heterochromatin, carcinogen-modified DNA was examined by stepwise or caffeine gradient elution from benzoylated DEAE-cellulose. In whole DNA, nitrosamine-induced single-stranded character was maximal 4-24 h after treatment, declining rapidly thereafter; gradient elution of these DNA preparations also provided short-term evidence of structural change. Caffeine gradient chromatography suggested short-term nitrosamine-induced structural change in euchromatic DNA, while increased binding of heterochromatic DNA was evident for up to 3 months after carcinogen treatment. Preparations of newly synthesized heterochromatic DNA from animals subjected to hepatectomy up to 2 months after carcinogen treatment provided evidence of heritable structural damage. Carcinogen-induced binding of heterochromatic DNA to benzoylated DEAE-cellulose was indicative of specific structural lesions whose affinity equalled that of single-stranded DNA up to 1.0 kilobase in length. The data suggest that structural lesions in heterochromatin, which may be a consequence of incomplete repair, are preferentially degraded by endogenous nuclease(s).
- Research Organization:
- Univ. of New South Wales, Kensington, Australia
- OSTI ID:
- 6407119
- Journal Information:
- Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:6; ISSN BICHA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANALEPTICS
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CAFFEINE
CENTRAL NERVOUS SYSTEM AGENTS
CHROMATIN
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DNA
DNA REPAIR
DRUGS
GENETIC EFFECTS
GLANDS
HETEROCHROMATIN
HETEROCYCLIC COMPOUNDS
ION EXCHANGE CHROMATOGRAPHY
LABELLED COMPOUNDS
LIVER
MAMMALS
MOLECULAR STRUCTURE
NITROSO COMPOUNDS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PURINES
PYRIMIDINES
RATS
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SEPARATION PROCESSES
STRAND BREAKS
THYMIDINE
TRITIUM COMPOUNDS
VERTEBRATES
XANTHINES