Oxidative Stress on Liver Tissue: Damage in Liver Chromatin by Oxygen Free Radicals Generated from Reaction of Hydrogen Peroxide with Copper or Iron Ions

Abstract

We examined the susceptibility of liver chromatin of mice at prenatally 16-days (fetus) and postnatally 19~23-weeks (adult) for hydroxyl radical (・OH). DNA strand breakages in both fetal and adult liver nuclei by Cu (II) -H₂O₂ system were shown to be more extensive that that by Fe (III) -H₂O₂ system under the same experimental conditions. DNA damage in nuclei also showed higher rate and extent in fetal liver than that of adult, especially for oxidation by Cu (II) -H₂O₂ system. The reduced glutathione (GSH), N-acetylcysteine (NAC) and ascorbic acid (ASC) showed the promotive effects on DNA damages by ・OH, whereas cysteine (CYS) showed the antioxidative effect. In fetal liver, 5-methylcytosine (5mC) contents in chromatin were less than that of adult, suggesting the active chromatin structure in fetal liver nuclei. The increase of DNA damage by ・OH in fetal liver nuclei which accompanied the expansion of chromatin, indicated the importance of chromatin compaction for the oxygen free radical injury. The results also suggested that Cu (II) and Fe (III) ions act at different nuclei loci, and that Cu (II) ion binds to unmethylated sites on DNA constructing the nuclear matrix.