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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

Journal Article · · Carcinogenesis (N.Y.); (United States)
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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), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 6:1; ISSN CRNGD
Country of Publication:
United States
Language:
English

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Related Subjects

550501 -- Metabolism-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AMINES
ANILINE
ANIMAL TISSUES
ANIMALS
AROMATICS
AZINES
BIOSYNTHESIS
BODY
CARCINOGENS
CHEMICAL BONDS
CHROMATOGRAPHY
COVALENCE
DIGESTIVE SYSTEM
DISEASES
DNA
DNA ADDUCTS
EPITHELIUM
GASTROINTESTINAL TRACT
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROXAMIC ACIDS
HYDROXY COMPOUNDS
IN VIVO
INTESTINES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MAMMALS
NEOPLASMS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRIMIDINES
RATS
RIBOSIDES
RNA
RODENTS
SEPARATION PROCESSES
SYNTHESIS
THYMIDINE
TISSUES
TOXICITY
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES