DNA Chemically Modified by N-Acetoxy-N-2-Acetyl-Aminofluorene : Nature of the Adducts and Conformation of the Modified DNA
Two aspects of chemical modifications of DNA by aminofluorene derivatives are considered. On one hand, it is shown that the covalent binding of AAF residues to the C(8) of guanine residues can induce a conformational change of poly(dG.dC).poly(dG.dC) from the B-form to the Z-form or a Z-like form. On the other hand, the presence of a deacetylated adduct in liver DNA of rats treated with the carcindgen is demonstrated by the use of specific antibodies.
Chemical carcinogens can react with nucleic acids and proteins. Until now, most of the works have been devoted to the reaction with DNA. The covalent binding of the carcinogens to DNA can modify the conformation of DNA and consequently the interactions between the modified DNA and some proteins. This might be important in the tumorogenic process. This assumption is the basis of our work on DNA modified by aminofluorene derivatives.
In the in vivo reaction between N-acetoxy-N-2-acetyl-amino-fluorene (N-AcO-AAF) and DNA, several adducts are formed. Two of them have been identified as N-(deoxyguanosin-8-yl)-acetylaminofluorene and as 3(deoxyguanosin-N-2-yl)-acetylaminofluorene and they represent about 30% of the total adducts. The other adducts (about 70%) are not yet completely identified. However, it is known that the acetyl groups (on the nitrogen of the aminofluorene residues) are removed. The acetylated adducts are also formed in vitro by the non enzymatic reaction between DNA and N-AcO-AAF (general review 1).
In this paper, we report two aspects of our work. On one hand, it is shown that specific antibodies can be used to identify and to titrate some adducts. On the other hand, the conformation of modified model DNA (poly(dC.dC).poly(dG.dC)) has been studied by circular dichroism.
KeywordsAdenosine Adduct Fluorene Acetyl Aspergillus
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