Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro

Djelić, Ninoslav; Spremo-Potparević, Biljana; Bajić, Vladan; Djelic, Dijana

doi:10.1016/j.mrgentox.2005.11.013

Cited by 14 publications

(20 citation statements)

References 32 publications

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“…Thus, the overall percentage of aberrant cells in L-thyroxine treated cultures was in the range of 0% to 4.5% and there was no significant departure (p > 0.05) form the negative control base level. This agrees with our previous investigations (Djelic et al, 2006) in which we observed no significant effect in the cytokinesis block micronucleus assay, using blood samples from the same donors and the same assay conditions. As expected, the positive control (MNNG) caused significant clastogenic effects, detectable as an increase in breaks and chromatid and isochromatid exchanges (p < 0.001), indicating that the experimental conditions were suitable for detecting clastogenic effects.…”

supporting

confidence: 93%

“…Our results show that L-thyroxine did not produce clastogenic effects which could be detected on the basis of cytogenetic analysis and supports previous observations that L-thyroxine does not cause any significant increase in the micronucleus frequency of human peripheral blood lymphocytes (Djelic et al, 2006). However, it should be pointed out that thyroid hormones caused DNA damage in the comet assay, at high concentrations in a range 10-100 μM (Djelic and Anderson, 2003;Dobrzynska et al, 2004).…”

supporting

confidence: 91%

“…The suggestion that L-thyroxine can have genotoxic effects is supported by reports of increased SCE in human lymphocytes treated with relatively high concentrations of L-thyroxine, although since L-thyroxine did not induce micronuclei under the same experimental conditions the cytogenetic effects of L-thyroxine were unclear (Djelic et al, 2006). It is important to note, however, that in the study by Djelic and Anderson (2003) the DNA damage attributed to thyroid hormones was detected by the comet assay of purified human lymphocytes, with the cytogenetic evaluation of the genotoxic effects of L-thyroxine on lymphocytes from whole blood cultures producing equivocal results.…”

mentioning

confidence: 97%

“…Since the antioxidant enzyme catalase reduced these effects, DNA damage was caused mainly by action of ROS. In our previous investigations, we also studied the cytogenetic effects of L-thyroxine on human peripheral blood lymphocytes by monitoring sister-chromatid exchange (SCE) and micronuclei as endpoints of the genotoxic exposure (Djelic et al, 2006). However, thyroxine exhibited only weak genotoxic effects expressed as an increased frequency of SCE per cell in cultured human lymphocytes, whereas no effect was observed in the cytokinesis block micronucleus assay (Djelic et al, 2006).…”

mentioning

confidence: 99%

“…In our previous investigations, we also studied the cytogenetic effects of L-thyroxine on human peripheral blood lymphocytes by monitoring sister-chromatid exchange (SCE) and micronuclei as endpoints of the genotoxic exposure (Djelic et al, 2006). However, thyroxine exhibited only weak genotoxic effects expressed as an increased frequency of SCE per cell in cultured human lymphocytes, whereas no effect was observed in the cytokinesis block micronucleus assay (Djelic et al, 2006). Since these results of cytogenetic evaluation of thyroxine toxicity were equivocal, we undertook the investigation described in this paper to further elucidate possible clastogenic effects of thyroxine on cultured human lymphocytes.…”

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confidence: 99%

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Lack of clastogenic effects of L-thyroxine in whole-blood cultured human lymphocytes

et al. 2007

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Thyroid hormones stimulate aerobic metabolism which may lead to oxidative stress accompanied by damage to various cellular macromolecules, including DNA. Previous comet assay studies have shown that thyroid hormones cause DNA damage due to the creation of reactive oxygen species (ROS). However, cytogenetic studies have been equivocal because although an increase in the sister-chromatid exchange frequency per cell has been reported increased micronuclei frequency has not. We used cytogenetic examination of chromosome breakage and aberrations in whole-blood cultures of human peripheral blood lymphocytes to investigate possible clastogenic effects when lymphocytes were exposed to 0.002 μM to 50 μM of L-thyroxine for 24 h and 48 h, these concentrations being chosen because they had been used in previous studies of sister-chromatid exchange and micronuclei frequency. Under our experimental conditions thyroxine did not induced any statistically significant increase in chromosome breakage or aberrations. This lack of clastogenic effects is in contrast to the reported comet assay results obtained using purified lymphocytes, possibly because whole-blood cultures contain catalase and glutathione peroxidase capable of reducing the effects of reactive oxygen species.

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supporting

confidence: 93%

supporting

confidence: 91%

mentioning

confidence: 97%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Lack of clastogenic effects of L-thyroxine in whole-blood cultured human lymphocytes

et al. 2007

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Effect of l-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions

et al. 2015

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The aim was to study the genotoxic effect of high concentration of thyroxine (T4) in vivo in peripheral blood lymphocytes (PBL) of the patients suffering from thyroid disorders. The effect was compared by performing in vitro experiments with addition of increasing concentration of T4 (0.125-1 µM) in whole blood samples from healthy donors. Cytokinesis-blocked micronuclei (CBMN) assay method was used to assess the DNA damage in the PBL. The study included 104 patients which were grouped as control (n = 49), hyperthyroid (n = 31) and hypothyroid (n = 24). A significant increase in micronuclei (MN) frequency was observed in hyperthyroid patients when compared with the hypothyroid and euthyroid group thereby suggesting increased genotoxicity in hyperthyroidism (p < 0.001). A significant increase in MN frequency was observed at T4 concentration of 0.5 µM and above when compared to lower T4 concentrations (0.125 and 0.25 µM) and basal in in vitro experiments (p = 0.000). The results indicate that the T4 in normal concentration does not exhibit the genotoxic effect, as observed in both the in vivo and in vitro experiments. The toxicity of T4 increases at and above 0.5 μM concentration in vitro. Therefore acute T4 overdose should be handled promptly and effectively so as to avoid the possible genotoxic effect of high concentration of T4 in vivo.

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Mutagenicity and Carcinogenicity of African Medicinal Plants

Tamokou¹,

Kuete²

2014

Toxicological Survey of African Medicinal Plants

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Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro

Cited by 14 publications

References 32 publications

Lack of clastogenic effects of L-thyroxine in whole-blood cultured human lymphocytes

Lack of clastogenic effects of L-thyroxine in whole-blood cultured human lymphocytes

Effect of l-Thyroxine on Micronuclei Frequency in Peripheral Blood Lymphocytes in Clinical and Experimental Conditions

Mutagenicity and Carcinogenicity of African Medicinal Plants

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