鉄イオンおよび鉄錯体によるDNA鎖切断

概要

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Ferric nitrilotriacetate (Fe^<3+>-NTA) is an iron complex. Repeated injections of Fe^<3+>-NTA in experimental animals induce iron overload and injuries of several organs. Fe^<3+>-NTA is also a potent carcinogen and has been shown to cause renal cell carinoma in the rat. In the present study, we investigated DNA strand breaks induced by Fe^<3+>-NTA in vitro by use of supercoiled closed circular DNA of plasmid pUC 19. The conformational change of DNA caused by a singel strand or double strand DNA break was easily detected by agarose gle electrophoresis. The DNA strand breaks were not observed with Fe^<3+>-NTA alone. However in the presence of 10mM hydrogen peroxide or 10mM dithiothreitol Fe^<3+>-NTA, at more than 10^<-4>M, caused DNA cleavage. Decrease of form I DNA and increase of form II and form III DNAs were observed by raising the Fe^<3+>-NTA concentration in the reaction. The requirement of hydrogen peroxide for the cleavage of DNA by Fe^<3+>-NTA suggested that Fe^<3+>-NTA catalyzed the production of hydroxyl radicals from hydrogen peroxide and the radicals caused the DNA strand breaks.
岡山理科大学の論文