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), Vol. 26:6
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
HETEROCHROMATIN
MOLECULAR STRUCTURE
NITROSO COMPOUNDS
GENETIC EFFECTS
AMINES
CAFFEINE
DNA
DNA REPAIR
ION EXCHANGE CHROMATOGRAPHY
LIVER
RATS
STRAND BREAKS
THYMIDINE
TRITIUM COMPOUNDS
ANALEPTICS
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CENTRAL NERVOUS SYSTEM AGENTS
CHROMATIN
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DRUGS
GLANDS
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PURINES
PYRIMIDINES
RECOVERY
REPAIR
RIBOSIDES
RODENTS
SEPARATION PROCESSES
VERTEBRATES
XANTHINES
560300* - Chemicals Metabolism & Toxicology
550201 - Biochemistry- Tracer Techniques