環境から分離した新規変異原物質のDNA修飾に関する研究(研究奨励賞, 第33回大会受賞講演)

概要

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Three areas recently researched on DNA adducts derived from environmental mutagens are described in this paper. (1) A new type of DNA adduct was obtained from 3-nitrobenzanthrone, a powerful mutagen present in the atmospheric environment. N-acetoxy-N-acetyl-3-aminobenzanthrone, a metabolic ultimate form of 3-nitrobenzanthrone, was found to react with 2'-deoxyguanosine to generate N-acetyl-2-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone, where the C8 position of guanosine is covalently bound to the C2 position of the benzanthrone moiety. This C-C bond formation structure is vastly different from the general C-N bond type DNA adducts formed with amino/nitroarenes. (2) ADP-ribosylation of nucleic acids was reported. Pierisin-1 is a cytotoxic protein present in pupa of cabbage butterflies, and has been shown to have ADP-ribosyltrans-ferase activity, targeting DNA molecules. The N^2 position of guanosine is ADP-ribosylated to form N^2-(ADP-ribos-1-yl)-2'-deoxyguanosine. (3) The last topic described is the general method for generating so-called dG-C8 adducts derived from amino/nitroarenes. Fully protected 8-amino-2'-deoxyguanosine was able to couple with several bromoarenes to form a protected dG-C8 adduct under the condition of arylamination catalyzed by Pd. This procedure can be used for the preparation of authentic samples of dG-C8 adducts or synthesis of a site-specific adducted oligonucleotide.
日本環境変異原学会の論文
2005-04-15