Abstract
Background
A high dissolution of copper from intrauterine devices (IUDs) occurs during the first
days after insertion. This work is focused on the assessment of the possible cyto-
and genotoxic effects of different concentrations of copper ions released from metallic
copper on mammalian cells in vitro.
Study Design
Colorimetric tetrazolium/Trypan blue (TB) tests and Comet assay were used to evaluate
potential cytotoxicity and genotoxicity, respectively, in Chinese hamster ovary cells
(CHO-K1).
Results
Reduction of mitochondrial activity by copper ions was observed for extracts at ���7.42
mg/L concentrations, while TB exclusion test for plasma membrane integrity showed
significant decrease in cell viability (close to 90%) for 10.85 mg/L concentration.
Additionally, copper-induced DNA damage was detected for 5.67���7.42 mg/L concentration
range.
Conclusion
Our results demonstrate cytotoxic and genotoxic effects of copper ions released from
metallic copper on CHO-K1 cells and emphasize the importance of reducing the initial
copper dissolution from IUD without affecting the contraceptive action.
Keywords
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References
- Uterine factors and risk of pregnancy in IUD users: a nested case-control study.Contraception. 2003; 67: 235-239
- Contraception through the use of intrauterine metals. I. Copper as an adjunct to the T device.Am J Obstet Gynecol. 1979; 109: 771-774
- Formation of copper oxychloride and reactive oxygen species as causes of uterine injury during copper oxidation of Cu-IUD.Contraception. 2000; 61: 99-103
- Characterization of copper in uterine fluids of patients who use the copper T-380A intrauterine device.Clinica Chim Acta. 2003; 332: 69-78
- Copper IUD and LNG IUD compared with tubal occlusion.Contraception. 2007; 75: 144-151
- Systemic absorption of intrauterine copper.Science. 1972; 177: 358-361
- Serum and endometrial copper, zinc, iron and cobalt with inert and copper-containing IUCDs.Contraception. 1993; 47: 483-490
- Blood copper levels in Mexican users of the T380A IUD.Contraception. 2005; 72: 122-125
- Influence of pH and oxygen on copper corrosion in simulated uterine fluid.Biomaterials. 2002; 23: 667-671
- Copper corrosion-simulated uterine solutions.Contraception. 2000; 61: 395-399
- Local tissue effects of copper-containing intrauterine devices.Fertil Steril. 2003; 80: 1281-1283
- Copper and carcinogenesis.Crit Rev Oncol Hematol. 2002; 42: 57-64
- Copper-DNA adducts.Methods Enzymol. 1994; 234: 66-79
- Copper induces histone hypoacetylation through directly inhibiting histone acetyltransferase activity.Chem Biol Interact. 2004; 148: 115-123
- Possible mechanisms underlying copper-induced damage in biological membranes leading to cellular toxicity.Chem Biol Interact. 2005; 151: 71-82
- A comparison of hepatocyte cytotoxic mechanisms for Cu2+ and Cd2+.Toxicology. 2000; 143: 263-273
- Copper toxicity, oxidative stress and antioxidant nutrients.Toxicology. 2003; 189: 147-163
- Effects of mixing metal ions on oxidative DNA damage mediated by a Fenton-type reduction.Toxicol Vitro. 2008; 22: 36-44
- Copper ions differ from other thiol reactive metal ions in their effects on the concentration and redox status of thiols in HeLa cell cultures.Toxicology. 1997; 117: 89-97
- Oxidative stress in chemical toxicity.Arch Toxicol. 1987; 60: 144-149
- Neoplasia with use of intrauterine devices.Contraception. 2007; 75: 60-69
- Meta-analysis of intrauterine device use and risk of endometrial cancer.Ann Epidemiol. 2008; 18: 492-499
- The single cell gel/Comet assay: guidelines for in vitro and in vivo genetic toxicology testing.Environ Mol Mutagen. 2000; 35: 206-221
- Influence of cytotoxicity and compound precipitation on test results in the alkaline Comet assay.Mutat Res. 2001; 497: 199-212
- Rapid colorimetric assay for cellular growth and cytotoxicity assays.J Immunol Meth. 1983; 65: 55-63
- A study of some variables in a tetrazolium dye (MTT) based assay for cell growth and chemosensitivity.Br J Cancer. 1987; 56: 279-285
- Trypan blue exclusion test of cell viability.in: Coligan J. Kruisbeek A. Marguiles D. Shevach E. Strober W. Current protocols immunology. John Wiley & Song, New York2003: A-3B
- A simple technique for quantification of low levels of DNA damage in individual cells.Exp Cell Res. 1988; 175: 184-191
- The single cell gel electrophoresis/Comet assay: a potential tool for detecting radiation-induced DNA damage in humans.Stem Cells. 1995; 13: 207-214
- SYBR Green I and the improved sensitivity of the single-cell electrophoresis assay.Int J Radiat Biol. 2000; 76: 61-65
- The Comet assay: a new method to examine heterogeneity associated with solid tumors.Nature Med. 1988; 4: 103-105
- DNA damage and repair in individual cells: applications of the Comet assay in radiobiology.Int J Radiat Res. 1996; 75: 395-405
- Revalidation of the in vitro alkaline elution/rat hepatocyte assay for DNA damage: improved criteria for assessment of cytotoxicity and genotoxicity and results for 81 compounds.Mutat Res. 1996; 368: 59-101
- Zinc acetate for the treatment of Wilson's disease.Expert Op Pharmacother. 2001; 2: 1473-1477
- Evaluation of copper toxicity in isolated human peripheral blood mononuclear cells and its attenuation by zinc: ex vivo.Mol Cell Biochem. 2006; 282: 13-21
- The corrosion behavior of copper in simulated uterine fluid corrosion.Science. 1996; 38: 635-641
- Corrosion behavior of copper/LDPE nanocomposites in simulated uterine solution.Biomaterials. 2005; 26: 2671-2676
- Can intrauterine device removals for bleeding or pain be predicted at a one-month follow-up visit?.Contraception. 1998; 58: 357-360
- Fern��ndez Lorenzo de Mele M. Effects of copper ions released from metallic copper on CHO-K1 cells.Mutat Res. 2009; 672: 45-50
- Fern��ndez Lorenzo de Mele M. Relationship between radial difusion of copper ions released from a metal disk and cytotoxic effects. Comparison with results obtained using extracts.Bioelectrochemistry. 2008; 72: 94-101
- Hormesis effect of trace metals on cultured normal and immortal human mammary cells.Toxicol Ind Health. 2004; 20: 57-68
- Fundamental flaws of hormesis for public health decisions.Environ Health Perspect. 2005; 113: 1271-1276
- In vitro assessment of copper-induced toxicity in human hepatoma line, Hep G2.Toxicol In Vitro. 2004; 18: 501-509
Article info
Publication history
Published online: January 15, 2010
Accepted:
December 4,
2009
Received in revised form:
December 2,
2009
Received:
October 20,
2009
Identification
Copyright
© 2010 Elsevier Inc. Published by Elsevier Inc. All rights reserved.