Biomaterial Database

DNA cleavage by hydroxyl radicals generated in the Cu,Zn-superoxide dismutase and hydrogen peroxide system. 1997

J H Kang, and S M Kim

Department of Genetic Engineering, Chongju University, Korea.

To study the catalytic activity of Cu,Zn-superoxide dismutase (SOD) in the generation of hydroxyl radical (.OH) from H2O2, we investigated the mechanism of DNA cleavage mediated by human Cu,Zn-SOD and H2O2. When plasmid DNA was incubated with 5 microM Cu, Zn-SOD and 1.0 mM H2O2, DNA cleavage occurred within 15 min. A spectrophotometric study using a 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS) showed that free .OH formation was proportional to concentrations of Cu,Zn-SOD and H2O2. .OH formation and DNA cleavage were inhibited by hydroxyl radical scavengers such as cyanide, azide, and formate. These results indicated that .OH generated early in the peroxidative reaction of Cu,Zn-SOD with H2O2 was implicated in DNA cleavage. Incubation with H2O2 resulted in a time-dependent release of copper ions from the Cu,Zn-SOD molecule. The released copper ions then likely participated in a Fenton-like reaction to produce .OH that may have caused DNA cleavage. Evidence that DTPA protected the DNA cleavage induced by the Cu,Zn-SOD/H2O2 system supports this mechanism. We suggest that DNA cleavage is mediated in the Cu,Zn-SOD/H2O2 system via the generation of .OH by a combination of the peroxidative reaction of Cu,Zn-SOD and the Fenton-like reaction of free copper ions released from oxidatively damaged SOD.

UI	MeSH Term	Description	Entries
D007202	Indicators and Reagents	Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499)	Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D009690	Nucleic Acid Conformation	The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.	DNA Conformation,RNA Conformation,Conformation, DNA,Conformation, Nucleic Acid,Conformation, RNA,Conformations, DNA,Conformations, Nucleic Acid,Conformations, RNA,DNA Conformations,Nucleic Acid Conformations,RNA Conformations
D010957	Plasmids	Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.	Episomes,Episome,Plasmid
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D003486	Cyanides	Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical.	Cyanide,Isocyanide,Isocyanides
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004369	Pentetic Acid	An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium.	DTPA,Diethylenetriamine Pentaacetic Acid,Pentetates,Penthanil,Ca-DTPA,CaDTPA,CaNa-DTPA,Calcium Trisodium Pentetate,DETAPAC,Indium-DTPA,Mn-Dtpa,Pentacin,Pentacine,Pentaind,Pentetate Calcium Trisodium,Pentetate Zinc Trisodium,Sn-DTPA,Zinc-DTPA,Indium DTPA,Pentaacetic Acid, Diethylenetriamine,Pentetate, Calcium Trisodium,Zinc DTPA
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006861	Hydrogen Peroxide	A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials.	Hydrogen Peroxide (H2O2),Hydroperoxide,Oxydol,Perhydrol,Superoxol,Peroxide, Hydrogen