Histone H1- and other protein- and amino acid-hydroperoxides can give rise to free radicals which oxidize DNA.

摘要: Exposure of amino acids, peptides and proteins to radicals, in the presence oxygen, gives high yields hydroperoxides. These materials are readily decomposed by transition metal ions give further radicals. We hypothesized that hydroperoxide formation on nuclear proteins, subsequent decomposition these hydroperoxides might result oxidative damage associated DNA. demonstrate here exposure histone H1 model compounds gamma-radiation oxygen a dose-dependent manner. decompose oxygen- carbon-centred radicals (detected electron paramagnetic resonance spectroscopy) Cu(+) other ions. hydroperoxide-derived react with pyrimidine DNA bases nucleosides adduct species (i.e. protein-DNA base cross-links). Product analysis has demonstrated from H1-hydroperoxides, protein acid hydroperoxides, can also oxidize both free 2'-deoxyguanosine intact calf thymus mutagenic oxidized 7, 8-dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine, 8-oxodG). The yield 7,8-dihydro-8-oxo-2'-deoxyguanosine is proportional initial protein-hydroperoxide concentration, corresponds (for H1-hydroperoxide, 280 microM) approx. 1. 4% conversion for (200 microM), 0.14% (70 microgram/ml). Evidence been obtained reaction at cytosine thymine, but not adenine; lack latter may transfer residues. studies radical-induced rise damage; includes DNA-protein cross-links bases.