Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl, and 2-acetylaminophenanthrene

Journal Article · Thu Mar 01 04:00:00 EST 1984 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/5.3.343· OSTI ID:6903854

Gupta, R C; Dighe, N R

Formation and removal of hepatic DNA adducts was studied in male Sprague-Dawley rats following single injections of two hepatocarcinogens, N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) and a nonhepatocarcinogen, N-hydroxy-2-acetylaminophenanthrene (N-OH-AAP) at 0.5 h, 1.5 h, 4 h, 24 h, 9 d and 29 d. Using a previously described /sup 32/P-postlabeling assay, maximal DNA binding of these compounds was observed at approximately 1.5 h, 0.5 h and 24 h, respectively. In addition to the formation of three already known C8- and N2-acetylated and C8-deacetylated guanine derivatives and several minor unknown adducts with N-OH-AAF, a set of four new major adducts was also detected. These comprised approximately 50% of the total adducts during the first 4 h. The three known adducts amounted to 58, 16 and 6% of the 1.5-h value after 24 h, 9 d and 29 d, respectively, while the bulk (greater than 84%) of the new major adducts were removed from the DNA within 24 h and found only in traces after 9 d. N-OH-AABP formed several unknown minor adducts, in addition to the one major C8-deacetylated and two minor C8- and N2-acetylated guanine derivatives; only the C8-deacetylated and N2-acetylated adducts were detected after 29 d. In the case of N-OH-AAP, two major and several minor adducts were detected, most of which were found to be deacetylated, and as much as 60% of the adducts measured at 24 h were still present after 9 d treatment. These data indicate that certain DNA adducts are repaired rapidly, while others persist for long periods.

• Research Organization: Department of Pharmacology, Baylor College of Medicine, Texas Medical Center, Houston
• OSTI ID: 6903854
• Journal Information: Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 5:3; ISSN CRNGD
• Country of Publication: United States
• Language: English

Related Subjects

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560301* -- Chemicals Metabolism & Toxicology-- Cells-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CHEMICAL BONDS
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
DNA
DNA ADDUCTS
DOSE-RESPONSE RELATIONSHIPS
FLUORENE
HYDROCARBONS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHENANTHRENE
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
REMOVAL
TRACER TECHNIQUES