TY - JOUR
T1 - Preventing Metal-Mediated Oxidative DNA Damage by Selenium Compounds
AU - Battin, Erin E.
AU - Zimmerman, Matthew T.
AU - Ramoutar, Ria R.
AU - Quarles, Carolyn E.
AU - Brumaghim, Julia L.
PY - 2011
Y1 - 2011
N2 - Copper and iron are two widely studied transition metals associated with hydroxyl radical (˙OH) generation, oxidative damage, and disease development. Because antioxidants ameliorate metal-mediated DNA damage, DNA gel electrophoresis assays were used to quantify the ability of ten selenium-containing compounds to inhibit metal-mediated DNA damage by hydroxyl radical. In the CuI/H2O2 system, selenocystine, selenomethionine, and methyl-selenocysteine inhibit DNA damage with IC50 values ranging from 3.34 to 25.1 μM. Four selenium compounds also prevent DNA damage from FeII and H2O2. Additional gel electrophoresis experiments indicate that CuI or FeII coordination is responsible for the selenium antioxidant activity. Mass spectrometry studies show that a 1 : 1 stoichiometry is the most common for iron and copper complexes of the tested compounds, even if no antioxidant activity is observed, suggesting that metal coordination is necessary but not sufficient for selenium antioxidant activity. A majority of the selenium compounds are electroactive, regardless of antioxidant activity, and the glutathione peroxidase activities of the selenium compounds show no correlation to DNA damage inhibition. Thus, metal binding is a primary mechanism of selenium antioxidant activity, and both the chemical functionality of the selenium compound and the metal ion generating damaging hydroxyl radical significantly affect selenium antioxidant behavior.
AB - Copper and iron are two widely studied transition metals associated with hydroxyl radical (˙OH) generation, oxidative damage, and disease development. Because antioxidants ameliorate metal-mediated DNA damage, DNA gel electrophoresis assays were used to quantify the ability of ten selenium-containing compounds to inhibit metal-mediated DNA damage by hydroxyl radical. In the CuI/H2O2 system, selenocystine, selenomethionine, and methyl-selenocysteine inhibit DNA damage with IC50 values ranging from 3.34 to 25.1 μM. Four selenium compounds also prevent DNA damage from FeII and H2O2. Additional gel electrophoresis experiments indicate that CuI or FeII coordination is responsible for the selenium antioxidant activity. Mass spectrometry studies show that a 1 : 1 stoichiometry is the most common for iron and copper complexes of the tested compounds, even if no antioxidant activity is observed, suggesting that metal coordination is necessary but not sufficient for selenium antioxidant activity. A majority of the selenium compounds are electroactive, regardless of antioxidant activity, and the glutathione peroxidase activities of the selenium compounds show no correlation to DNA damage inhibition. Thus, metal binding is a primary mechanism of selenium antioxidant activity, and both the chemical functionality of the selenium compound and the metal ion generating damaging hydroxyl radical significantly affect selenium antioxidant behavior.
KW - Hydroxyl Radical Generation
KW - Metal-Mediated DNA Damage
UR - http://dx.doi.org/10.1039/C0MT00063A
M3 - Article
AN - SCOPUS:79955692994
SN - 1756-5901
VL - 3
JO - Metallomics
JF - Metallomics
ER -