Generation of a Carbon-Centered Radical with DNA-Breaking Activity from Mutagenic Fluorene-2-Diazonium Salt

概要

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Fluorene-2-diazonium salt (FD) is produced by the reaction of 2-amino fluorene with nitrite and is highly mutagenic to Salmonella typhimurium TA 98 and TA 100 strains without requiring metabolic activation. The reactivity of FD towards DNA and its components was investigated. FD was unstable around neutral pH being converted into a number of products including 2-hydroxyfluorene and fluorene. Electron spin resonance studies using spin-trapping agents, 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tertbutyl-α-phenylnitrone (PBN), revealed that the carbon-centered radical, i.e., the fluorene radical, was generated from FD. FD effectively damaged Guo, dGuo, Ado, dAdo, dThd and dCyd, as demonstrated by high performance liquid chromatography, and cleaved supercoiled and double-stranded linear DNA as shown by agarose gel electrophoresis. The single strand breaking of supercoiled DNA by FD was inhibited by the hydrogen donors, ethanol, 2-mercaptoethanol and cysteine, as well as a spin-trapping agent DMPO, indicating the participation of the carbon-centered radical generated from FD in the DNA strand breaking.
公益社団法人日本薬学会の論文
1994-10-31