Distribution of initial and persistent 2-acetylaminofluorene-induced DNA adducts within DNA loops

Journal Article · Tue Oct 01 04:00:00 EDT 1985 · Proc. Natl. Acad. Sci. U.S.A.; (United States)

DOI:https://doi.org/10.1073/pnas.82.19.6605· OSTI ID:6383047

Gupta, R C; Dighe, N R; Randerath, K; Smith, H C

The intranuclear distribution of initial and persistent DNA adducts induced in vivo after four weekly injections of the hepatocarcinogen 2-acetylaminofluorene was examined in rat liver by using a protocol that fractionates chromatin from various regions of each of the multiple nuclear DNA loops. Ten hours after the initial dose, two acetylated (N-acetyl-N-(deoxyguanosin-8-yl)-2-aminofluorene and 3-(deoxyguanosin-N/sup 2/-yl)-2-acetylaminofluorene) and one deacetylated (N-(deoxyguanosin-8-yl)-2-aminofluorene) adduct were detected by a /sup 32/P-labeling assay and were found to have a random genomic distribution, as evident by their relative concentrations in various chromatin fractions. These data suggest that all regions of the DNA loops are equally susceptible to adduct formation. A nonrandom persistence of the deacetylated adduct in the regions where the DNA loops are constrained by the nuclear matrix was evident by 6 days after the last dose and was markedly apparent by 60 days. In contrast, all chromatin fractions had equally inefficient removal of the N/sup 2/-acetylated adduct by 6 days as well as 60 days but had complete removal of the C8-acetylated adduct. These findings suggest that pronounced regional differences in adduct repair along the DNA loops may play a role in chemically induced hepatocarcinogenesis.

• Research Organization: Baylor College of Medicine, Houston, TX
• OSTI ID: 6383047
• Journal Information: Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 82:19; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550401 -- Genetics-- 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.
ACETYLAMINOFLUORENES
ADDUCTS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
BODY
CARCINOGENESIS
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DNA ADDUCTS
DNA REPAIR
GLANDS
IN VIVO
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
NUCLEI
ODD-ODD NUCLEI
ORGANS
PATHOGENESIS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
RATS
RECOVERY
REPAIR
RODENTS
TRACER TECHNIQUES
VERTEBRATES