Cytogenetic effects of copper-containing intrauterine contraceptive device (IUCD) on blood lymphocytes

Shubber, E. K.; Amin, Nada S; El-Adhami, B. H.

doi:10.1016/s1383-5718(98)00090-4

Cited by 11 publications

(7 citation statements)

References 16 publications

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“…In human use, elevated plasma concentrations of Cu in blood were shown to cause chromosomal aberrations in blood lymphocytes (Shubber et al 1998), when CuIUDs were used for over one year. Such positive correlations for long-term use of CuIUDs and DNA damage must be taken as a safety warning.…”

Section: Discussionmentioning

confidence: 99%

“…The resulting damaged uterine tissue might largely be removed by menstruation, often increasing the severity and time of menses (Beltran-Garcia et al 2000). Furthermore, the sustained daily release of Cu 2+ ions also causes chronic systemic exposure (De la Cruz et al 2005;Okereke et al 1972;Shubber et al 1998). For instance, irrespective of the age of the user or the length of time of using TCu380A, De la Cruz et al, reported the sustenance of nearly double the normal values for Cu concentration in blood (De la Cruz et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

118

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Sustained release of copper (Cu) ions from Cu-containing intrauterine devices (CuIUD) is quite efficient for contraception. However, the tissue surrounding the CuIUD is exposed to toxic Cu ion levels. The objective for this study was to quantify the concentration dependent cytotoxic effects of Cu ions and correlate the toxicity due to Cu ion burst release for two popular T-shaped IUDs - TCu380A and TCu220C on L929 mouse fibroblasts. Fibroblasts were cultured in 98 well tissue culture plates and 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphehyltetrazolium bromide (MTT) assay was used to determine their viability and proliferation as a function of time. For cell seeding numbers ranging from 10,000 to 100,000, a maximum culture time of 48 h was identified for fibroblasts without significant reduction in cell proliferation due to contact inhibition. Thus, for Cu cytotoxicity assays, a cell seeding density of 50,000 and a maximum culture time of 48 h in 96 well plates were used. 24 h after cell seeding, culture media were replaced with Cu ion containing media solutions of different concentrations, including 24 and 72 h extracts from TCuIUDs and incubated for a further 24 h. Cell viability decreased with increasing Cu ion concentration, with 30 % and 100 % reduction for 40 μg/ml and 100 μg/ml respectively at 24 h. The cytotoxic effects were further evaluated using light microscopy, apoptosis and cell cycle analysis assays. Fibroblasts became rounded and eventually detached from TCP surface due to Cu ion toxicity. A linear increase in apoptotic cell population with increasing Cu ion concentration was observed in the tested range of 0 to 50 μg/ml. Cell cycle analysis indicated the arrest of cell division for the tested 25 to 50 μg/ml Cu ion treatments. Among the TCuIUDs, TCu220C having 265 mm(2) Cu surface area released 9.08 ± 0.16 and 26.02 ± 0.25 μg/ml, while TCu380A having 400 mm(2) released 96.7 ± 0.11 and 159.3 ± 0.15 μg/ml respectively following 24 and 72 h extractions. The effects of TCuIUD extracts on viability, morphology, apoptosis and cell cycle assay on L929 mouse fibroblasts cells, were appropriate for their respective Cu ion concentrations. Thus, a concentration of about 46 μg/ml (~29 μM) was identified as the LD50 dose for L929 mouse fibroblasts when exposed for 24 h based on our MTT cell viability assay. The burst release of lethal concentration of Cu ions from TCu380A, especially at the implant site, is a cause of concern, and it is advisable to use TCuIUD designs that release Cu ions within cytotoxic limits yet therapeutic, similar to TCu220C.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Cao

Zheng

et al. 2012

Biomed Microdevices

118

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“…They observed a combination of high copper plasma level, chromosomal aberrations, and an increased frequency of sister chromatid exchange with a positive correlation between the long-term use of the IUDs and DNA damage. 36…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Functions, Oxidative Stress and DNA Damage in Workers of a Copper Processing Industry

Kumar¹,

Khaliq²,

Singh³

et al. 2016

Int J Occup Environ Med

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“…In addition, copper compounds have been shown to produce DNA strand breaks [30]. A study examining the effect of the use of copper-containing intrauterine contraceptive devices (IUCD) in 40 women for periods between 1 and 4 years demonstrated an increase in chromosomal aberrations and high frequencies of sister chromatid exchanges in blood lymphocytes from subjects using the IUCD compared to control subjects [31].…”

Section: Discussionmentioning

confidence: 99%

“…It is important to note, however, that both the IUCD and Wilson's disease studies [31,32] are associated with atypical circumstances and while it is well established that copper overload (as in Wilson's disease) can have adverse effects, there is no evidence to indicate that, in healthy individuals, levels of copper intakes associated with adverse effects would be achieved by dietary means alone.…”

Section: Discussionmentioning

confidence: 99%

Copper Supplementation Has No Effect on Markers of DNA Damage and Liver Function in Healthy Adults (FOODCUE Project)

et al. 2003

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Background/Aims: Copper is routinely used in the laboratory to promote oxidation in vitro. However, copper concentrations are million-fold higher than physiological concentrations and, in contrast, accumulating evidence suggests that copper may have an antioxidant role in vivo. The aim of this study was to provide data on how increased intake of copper affected mononuclear leukocyte DNA damage and liver function in healthy young free-living men and women. Methods: The study design was a double-blind repeated crossover trial with treatment and intervening placebo periods, each of 6 weeks’ duration. The following supplementations were given orally in sequence: CuSO₄ at a dose of 3 mg copper/day and copper amino acid chelates at doses of 3 and 6 mg copper/day. Oxidative DNA damage was assessed using a modification of the alkaline Comet assay incorporating an endonuclease III digestion step. The assessment of liver function was by measurement of the liver enzymes, alanine aminotransferase and L-γ-glutamyltransferase. Results: There was no significant alteration in mononuclear leukocyte DNA damage or on liver function after 6 weeks of copper supplementation at two doses (3 and 6 mg/day). Conclusions: Copper supplementation (giving total copper intake at the highest level of 7 mg/day) did not induce DNA damage or adversely affect liver function in healthy adults.

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Cytogenetic effects of copper-containing intrauterine contraceptive device (IUCD) on blood lymphocytes

Cited by 11 publications

References 16 publications

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Concentration-dependent cytotoxicity of copper ions on mouse fibroblasts in vitro: effects of copper ion release from TCu380A vs TCu220C intra-uterine devices

Pulmonary Functions, Oxidative Stress and DNA Damage in Workers of a Copper Processing Industry

Copper Supplementation Has No Effect on Markers of DNA Damage and Liver Function in Healthy Adults (FOODCUE Project)

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