scholarly journals Metallothionein protects DNA from oxidative damage

1993 ◽  
Vol 291 (1) ◽  
pp. 193-198 ◽  
Author(s):  
L S Chubatsu ◽  
R Meneghini
Keyword(s):  
Oxidative Damage ◽  
Hydroxyl Radical ◽  
Antioxidant Properties ◽  
Chinese Hamster ◽  
Simian Virus 40 ◽  
Radical Scavenger ◽  
Strand Scission ◽  
Chinese Hamster Cells ◽  
Dna Strand

Metallothionein (MT) is a potent hydroxyl radical scavenger but its antioxidant properties in vivo have not been defined. Most of the recent results indicate that it does not afford protection to cells against the lethal action of oxidative stress. However, the possibility that MT confers protection against oxidative damage to a specific cellular target, such as DNA, had not been considered. We compared V79 Chinese hamster cells enriched in and depleted of MT in terms of DNA-strand scission. Zinc induces an increase in MT content of V79 Chinese hamster cells, without concomitant increase in the GSH level. These induced cells are more resistant to the production of DNA-strand scission by H2O2 than the parental cells. Conversely, cells rendered partially deprived of MT, by transfection with a plasmid vector in which the MT-I cDNA is antisense oriented in relation to a simian virus 40 promoter, became more susceptible to the DNA-damaging action of H2O2. The transfected cells did not exhibit alterations of GSH, superoxide dismutase- and H2O2-destroying enzymes. Indirect immunofluorescence indicated that most of the MT was concentrated in the cell nucleus. Neither overexpression nor lower expression of MT resulted in differential resistance to the killing action of H2O2. However, the combined high nuclear concentration of MT and its excellent hydroxyl scavenger properties confer protection to DNA from hydroxyl radical attack.

scholarly journals Antioxidant and Pro-Oxidant Activities of Melatonin in the Presence of Copper and Polyphenols In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 903 ◽  
Author(s):  
Jiajia Wang ◽  
Xiaoxiao Wang ◽  
Yufeng He ◽  
Lijie Jia ◽  
Chung S. Yang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Hydroxyl Radical ◽  
Density Functional ◽  
Antioxidant Activities ◽  
Chelating Agent ◽  
Redox System ◽  
Radical Scavenger ◽  
Dual Function ◽  
High Concentrations

Melatonin is a well-documented antioxidant. Physicochemical analysis using the density functional theory suggests that melatonin is a copper chelating agent; however, experimental evidence is still in demand. The present study investigated the influence of melatonin on reactive oxygen species (ROS) generated from polyphenol autoxidation in the presence of copper. Surprisingly, we found that melatonin paradoxically enhanced ROS formation in a redox system containing low concentrations of copper and quercetin (Que) or (−)-epigallocatechin-3-gallate (EGCG), due to reduction of cupric to cuprous ion by melatonin. Addition of DNA to this system inhibited ROS production, because DNA bound to copper and inhibited copper reduction by melatonin. When melatonin was added to a system containing high concentrations of copper and Que or EGCG, it diminished hydroxyl radical formation as expected. Upon addition of DNA to high concentrations of copper and Que, this pro-oxidative system generated ROS and caused DNA damage. The DNA damage was not prevented by typical scavengers of hydroxyl radical DMSO or mannitol. Under these conditions, melatonin or bathocuproine disulfonate (a copper chelator) protected the DNA from damage by chelating copper. When melatonin was administered intraperitoneally to mice, it inhibited hepatotoxicity and DNA damage evoked by EGCG plus diethyldithiocarbamate (a copper ionophore). Overall, the present study demonstrates the pro-oxidant and antioxidant activities of melatonin in the redox system of copper and polyphenols. The pro-oxidant effect is inhibited by the presence of DNA, which prevents copper reduction by melatonin. Interestingly, in-vivo melatonin protects against copper/polyphenol-induced DNA damage probably via acting as a copper-chelating agent rather than a hydroxyl radical scavenger. Melatonin with a dual function of scavenging hydroxyl radical and chelating copper is a more reliable DNA guardian than antioxidants that only have a single function of scavenging hydroxyl radical.

DNA of simian virus 40 mutates Chinese hamster cells

1980 ◽  
Vol 65 (3-4) ◽  
pp. 293-309 ◽  
Author(s):  
M. Theile ◽  
S. Scherneck ◽  
E. Geissler
Keyword(s):  
Chinese Hamster ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Chinese Hamster Cells

DNA strand specificity for UV-induced mutations at the HPRT locus in chinese hamster cells

1991 ◽  
Vol 27 ◽  
pp. S62
Author(s):  
P. Menichini ◽  
H. Vrieling ◽  
J. Venema ◽  
A. Abbondandolo ◽  
A.A. van Zeeland
Keyword(s):  
Chinese Hamster ◽  
Induced Mutations ◽  
Chinese Hamster Cells ◽  
Hprt Locus ◽  
Dna Strand

scholarly journals V79 Chinese-hamster cells rendered resistant to high cadmium concentration also become resistant to oxidative stress

1988 ◽  
Vol 256 (2) ◽  
pp. 475-479 ◽  
Author(s):  
A C Mello-Filho ◽  
L S Chubatsu ◽  
R Meneghini
Keyword(s):  
Oxidative Stress ◽  
Xanthine Oxidase ◽  
Superoxide Anion ◽  
Cadmium Concentration ◽  
Antioxidant Properties ◽  
Chinese Hamster ◽  
Chinese Hamster Cells ◽  
Cell Basis ◽  
High Concentrations ◽  
Resistant Cells

Chinese hamster cells (V79) resistant to high concentrations of Cd2+ in the medium were obtained by using the procedure of Beach & Palmiter [(1981) Proc. Natl. Acad. Sci. U.S.A. 78, 2110-2114], which in mouse led to amplification of metallothionein (MT) genes and to an enrichment in cellular MT. The Cd-resistant V79 clones isolated were significantly more resistant than parental cells to oxidative stress by extracellular H2O2 or a mixture of H2O2 and superoxide anion (O2-) generated by xanthine oxidase plus acetaldehyde. On a per-cell basis, there was no difference between the two cells in their total H2O2-decomposing or O2-(-)dismutating activity. The most likely explanation is that an enrichment in MT content in the Cd-resistant cells was responsible for this effect, because of the antioxidant properties already described for this protein.

scholarly journals Copper-ion-dependent damage to the bases in DNA in the presence of hydrogen peroxide

1991 ◽  
Vol 273 (3) ◽  
pp. 601-604 ◽  
Author(s):  
O I Aruoma ◽  
B Halliwell ◽  
E Gajewski ◽  
M Dizdaroglu
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Copper Ion ◽  
Nitrilotriacetic Acid ◽  
Dna Bases ◽  
Radical Scavenger ◽  
Base Damage

Mixtures of Cu2+ and H2O2 at pH 7.4 caused damage to the bases in DNA greater than that caused by mixtures of Fe3+ and H2O2. Addition of ascorbic acid to the Cu2+/H2O2 system caused a very large increase in base damage, much greater than that produced by the Fe3+/H2O2/ascorbic acid system. The products of base damage in the presence of Cu2+ were typical products that have been shown to result from attack of hydroxyl radicals upon the DNA bases. Cytosine glycol, thymine glycol, 8-hydroxyadenine and especially 8-hydroxyguanine were the major products in both the Cu2+/H2O2 and the Cu2+/H2O2/ascorbic acid systems. Base damage in DNA by these systems was inhibited by the chelating agents EDTA and nitrilotriacetic acid and by catalase, but not by superoxide dismutase, nor by the hydroxyl-radical scavenger mannitol. It is proposed that Cu2+ ions bound to the DNA react with H2O2 and ascorbic acid to generate hydroxyl radicals, which then immediately attack the DNA bases in a site-specific manner. A hypoxanthine/xanthine oxidase system also caused damage to the DNA bases in the presence of Cu2+ ions. This was inhibited by superoxide dismutase and catalase. The high activity of Cu2+ ions, when compared with Fe3- ions, in causing hydroxyl-radical-dependent damage to DNA and to other biomolecules, means that the availability of Cu2+ ions in vivo must be carefully controlled.

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