Formation of DNA adducts in vivo in rat liver and intestinal epithelium after administration of the carcinogen 3,2'-dimethyl-4-aminobiphenyl and its hydroxamic acid
Administration of the /sup 3/H-labeled colon carcinogen, 3,2'-dimethyl-4-aminobiphenyl (DMABP) and its hydroxamic acid derivative, N-hydroxy-N-acetyl-DMABP, to male F344 rats resulted in high levels of covalent binding to hepatic and intestinal DNA, RNA and protein. For both compounds, binding to hepatic macromolecules was 2-4 times higher than in the intestine. High pressure liquid chromatographic analysis of the enzymatically hydrolyzed DNA from liver and intestinal epithelium indicated the presence of two carcinogen-DNA adducts: 5-(deoxyguanosin-N2-yl)-DMABP (15%), N-(deoxyguanosin-8-yl)-DMABP (50%), and a decomposition product of the latter (15%). N-acetylated adducts were not detected. When measured after 7 days, all adducts in the intestinal DNA had decreased by 70%, while only a 29% decrease had occurred in the hepatic DNA. To determine if the loss of DMABP products was a consequence of cell turnover or repair, rats were treated with (/sup 3/H)thymidine and DMABP, and the specific activity of hepatic liver and intestinal DNA was measured. Between 1 and 7 days only a slight decrease in (/sup 3/H)thymidine content occurred in hepatic DNA as compared with a 95% reduction in intestinal DNA. Thus, the higher rate of DNA synthesis in the intestine versus that in the liver may serve to promote fixation of the initiating lesion and account for the preferential induction of intestinal cancer by DMABP.
- Research Organization:
- National Center for Toxicological Research, Jefferson, AR
- OSTI ID:
- 5706179
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Vol. 6:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANILINE
TOXICITY
DNA ADDUCTS
BIOSYNTHESIS
HYDROXAMIC ACIDS
CARCINOGENS
CHEMICAL BONDS
COVALENCE
DNA
EPITHELIUM
IN VIVO
INTESTINES
LIQUID COLUMN CHROMATOGRAPHY
LIVER
NEOPLASMS
PROTEINS
RATS
RNA
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADDUCTS
AMINES
ANIMAL TISSUES
ANIMALS
AROMATICS
AZINES
BODY
CHROMATOGRAPHY
DIGESTIVE SYSTEM
DISEASES
GASTROINTESTINAL TRACT
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RIBOSIDES
RODENTS
SEPARATION PROCESSES
SYNTHESIS
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism & Toxicology- Vertebrates- (-1987)
550501 - Metabolism- Tracer Techniques