Rapid release of carcinogen-guanine adducts from DNA after reaction with N-acetoxy-2-acetylaminofluorene or N-benzoyloxy-N-methyl-4-aminoazobenzene
Reaction of N-benzoyloxy-N-methyl-4-aminoazobenzene (N-benzoyloxy-MAB) or N-acetoxy-N-acetyl-2-aminofluorene (N-acetoxy-AAF), model ultimate aromatic amine or amide carcinogens, with (purine-/sup 14/C)DNA at pH 7.4 or reaction of N-hydroxy-2-aminofluorene (N-hydroxy-AF) at pH 4.6 resulted in the rapid release of /sup 14/C-containing products not precipitable with the DNA. Four such products were obtained on reaction with N-acetoxy-AAF, two with N-hydroxy-AF, and six with N-benzoyloxy-MAB. Depending on the DNA sample used, the total amounts of /sup 14/C in these products from the reactions with N-benzoyloxy-MAB or N-acetoxy-AAF ranged from about 5% to as much as 30-40% of the amounts in the N-(deoxyguanosin-8-yl)-MAB or N-(deoxyguanosin-8-yl)-AFF residues in the DNA from the same reaction mixtures. Reactions with N-acetoxy-(acetyl-3H)AAF showed that the two major products retained the amide residue from the N-acetoxy-AAF. When the reactions were carried out with (guanine-(8-/sup 3/H; 8-/sup 14/C); adenine-(2,8-/sup 3/H; 8-/sup 14/C))DNA, the two major products formed from N-acetoxy-AAF and four products formed from N-benzoyloxy-MAB had very low /sup 3/H:/sup 14/C ratios; these ratios were those expected for guanine derivatives which had lost the 8-/sup 3/H. Studies on the major DNA adducts N-(deoxyguanosin-8-yl)-MAB and N-(deoxyguanosin-8-yl)-AAF indicated that the new adducts were not formed from these nucleosides. The data suggest that the two major AAF products and the four MAB adducts studied are guanine derivatives formed by depurination of N-7 substituted adducts in the DNA.
- Research Organization:
- McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison
- OSTI ID:
- 7089865
- Journal Information:
- Carcinogenesis (N.Y.); (United States), Journal Name: Carcinogenesis (N.Y.); (United States) Vol. 3:1; ISSN CRNGD
- Country of Publication:
- United States
- Language:
- English
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59 BASIC BIOLOGICAL SCIENCES
ADDUCTS
AROMATICS
BENZENE
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
CARCINOGENESIS
CARCINOGENS
CHEMICAL ANALYSIS
COMPARATIVE EVALUATIONS
DNA
ELEMENTS
FLUORINE
HALOGENS
HYDROCARBONS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
NONMETALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
PATHOGENESIS
PH VALUE
QUANTITATIVE CHEMICAL ANALYSIS
RIBOSIDES
TRITIUM COMPOUNDS