TY  - JOUR
AU  - Bajić, Vladan
AU  - Potparević, Biljana
AU  - Živković, Lada
AU  - Đelić, N
AU  - Smith, Mark A.
PY  - 2008
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1137
AB  - Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase anaphase transition separate in a non-random, sequential order. This sequence has been shown to be deregulated in aging cells, various tumors, syndromes of chromosome instability, following certain chemical inductions, as well as in AD. Over time, premature chromosome separation is both a result of, and a driving force behind, further cohesion impairment, activation of cyclin dependent kinases, and mitotic catastrophe-a vicious circle resulting in cellular degeneration and death.
T2  - Bioscience Hypotheses
T1  - Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?
VL  - 1
IS  - 3
SP  - 156
EP  - 161
DO  - 10.1016/j.bihy.2008.03.006
ER  - 

@article{
author = "Bajić, Vladan and Potparević, Biljana and Živković, Lada and Đelić, N and Smith, Mark A.",
year = "2008",
abstract = "Chromosomal involvement is a legitimate, yet not well understood, feature of Alzheimer disease (AD). Firstly, AD affects more women than men. Secondly, the amyloid-β protein precursor genetic mutations, responsible for a cohort of familial AD cases, reside on chromosome 21, the same chromosome responsible for the developmental disorder Down's syndrome. Thirdly, lymphocytes from AD patients display a novel chromosomal phenotype, namely premature centromere separation (PCS). Other documented morphological phenomena associated with AD include the occurrence of micronuclei, aneuploidy, binucleation, telomere instability, and cell cycle re-entry protein expression. Based on these events, here we present a novel hypothesis that the time dimension of cell cycle re-entry in AD is highly regulated by centromere cohesion dynamics. In view of the fact that neurons can re-enter the cell division cycle, our hypothesis predicts that alterations in the signaling pathway leading to premature cell death in neurons is a consequence of altered regulation of the separation of centromeres as a function of time. It is well known that centromeres in the metaphase anaphase transition separate in a non-random, sequential order. This sequence has been shown to be deregulated in aging cells, various tumors, syndromes of chromosome instability, following certain chemical inductions, as well as in AD. Over time, premature chromosome separation is both a result of, and a driving force behind, further cohesion impairment, activation of cyclin dependent kinases, and mitotic catastrophe-a vicious circle resulting in cellular degeneration and death.",
journal = "Bioscience Hypotheses",
title = "Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?",
volume = "1",
number = "3",
pages = "156-161",
doi = "10.1016/j.bihy.2008.03.006"
}

Bajić, V., Potparević, B., Živković, L., Đelić, N.,& Smith, M. A.. (2008). Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?. in Bioscience Hypotheses, 1(3), 156-161.
https://doi.org/10.1016/j.bihy.2008.03.006

Bajić V, Potparević B, Živković L, Đelić N, Smith MA. Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?. in Bioscience Hypotheses. 2008;1(3):156-161.
doi:10.1016/j.bihy.2008.03.006 .

Bajić, Vladan, Potparević, Biljana, Živković, Lada, Đelić, N, Smith, Mark A., "Is the time dimension of the cell cycle re-entry in AD regulated by centromere cohesion dynamics?" in Bioscience Hypotheses, 1, no. 3 (2008):156-161,
https://doi.org/10.1016/j.bihy.2008.03.006 . .

TY  - JOUR
AU  - Đelić, N
AU  - Potparević, Biljana
AU  - Bajić, Vladan
AU  - Đelić, D
PY  - 2006
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/851
AB  - Thyroid hormones enhance the metabolic rate and the aerobic metabolism favoring oxidative stress, which is accompanied by induction of damage to cellular macromolecules including the DNA. The aim of the present study was to investigate the ability of thyroxine to induce sister chromatid exchange and micronuclei, and to modulate cell-cycle kinetics in cultured human lymphocytes. Eight experimental concentrations of thyroxine were used, ranging from 2 x 10(-9) to 0.5 x 10(-4) M. Treatment with thyroxine increased the frequency of SCE per cell at the higher concentrations (1.5 x 10(-6), 0.5 10(-5), 1.5 x 10(-5) and 0.5 x 10(-4) M). On the other hand, there were no significant aneugenic and/or clastogenic effects observed in the cytokinesis-block micronucleus assay. The results show that thyroxine acted as a relatively weak clastogen compared with the positive control N-methyl-N '-nitro-N-nitrosoguanidine (MNNG). In addition to the genotoxic effects, two high concentrations of thyroxine decreased the mitotic index and caused cell-cycle delay. In conclusion, thyroxine exhibited weak clastogenic effects only at high concentrations. Therefore, effects in humans might appear in cases of acute thyroxine overdose.
PB  - Elsevier Science BV, Amsterdam
T2  - Mutation Research - Genetic Toxicology and Environmental Mutagenesis
T1  - Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro
VL  - 604
IS  - 1-2
SP  - 1
EP  - 7
DO  - 10.1016/j.mrgentox.2005.11.013
ER  - 

@article{
author = "Đelić, N and Potparević, Biljana and Bajić, Vladan and Đelić, D",
year = "2006",
abstract = "Thyroid hormones enhance the metabolic rate and the aerobic metabolism favoring oxidative stress, which is accompanied by induction of damage to cellular macromolecules including the DNA. The aim of the present study was to investigate the ability of thyroxine to induce sister chromatid exchange and micronuclei, and to modulate cell-cycle kinetics in cultured human lymphocytes. Eight experimental concentrations of thyroxine were used, ranging from 2 x 10(-9) to 0.5 x 10(-4) M. Treatment with thyroxine increased the frequency of SCE per cell at the higher concentrations (1.5 x 10(-6), 0.5 10(-5), 1.5 x 10(-5) and 0.5 x 10(-4) M). On the other hand, there were no significant aneugenic and/or clastogenic effects observed in the cytokinesis-block micronucleus assay. The results show that thyroxine acted as a relatively weak clastogen compared with the positive control N-methyl-N '-nitro-N-nitrosoguanidine (MNNG). In addition to the genotoxic effects, two high concentrations of thyroxine decreased the mitotic index and caused cell-cycle delay. In conclusion, thyroxine exhibited weak clastogenic effects only at high concentrations. Therefore, effects in humans might appear in cases of acute thyroxine overdose.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Mutation Research - Genetic Toxicology and Environmental Mutagenesis",
title = "Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro",
volume = "604",
number = "1-2",
pages = "1-7",
doi = "10.1016/j.mrgentox.2005.11.013"
}

Đelić, N., Potparević, B., Bajić, V.,& Đelić, D.. (2006). Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro. in Mutation Research - Genetic Toxicology and Environmental Mutagenesis
Elsevier Science BV, Amsterdam., 604(1-2), 1-7.
https://doi.org/10.1016/j.mrgentox.2005.11.013

Đelić N, Potparević B, Bajić V, Đelić D. Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro. in Mutation Research - Genetic Toxicology and Environmental Mutagenesis. 2006;604(1-2):1-7.
doi:10.1016/j.mrgentox.2005.11.013 .

Đelić, N, Potparević, Biljana, Bajić, Vladan, Đelić, D, "Sister chromatid exchange and micronuclei in human peripheral blood lymphocytes treated with thyroxine in vitro" in Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 604, no. 1-2 (2006):1-7,
https://doi.org/10.1016/j.mrgentox.2005.11.013 . .

TY  - JOUR
AU  - Đelić, N
AU  - Potparević, Biljana
AU  - Đelić, D
PY  - 2005
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/622
AB  - The objective of the present study was to evaluate possible genetic changes in cultured human lymphocytes treated with estradiol, using the cytokinesis block micronucleus assay. Eight experimental concentrations of estradiol were used (range from 10(-10) M to 0.7 x 10(-4) M). The obtained results indicate that estradiol exhibits aneugenic and/or clastogenic effects, expressed as increased frequency of micronucleated lymphocytes at two highest experimental concentrations used in this investigation. In addition to genotoxic effects, these concentrations decreased the cytokinesis block proliferation index (CBPI) and percentage of binucleated cells, indicating the cell cycle delay and possible cytotoxic effects. In conclusion, estradiol treatment might represent a human health risk, especially if overdosed or used for a prolonged period of time.
PB  - Akademiai Kiado, Budapest
T2  - Acta Biologica Hungarica
T1  - Mutagenic activity of estradiol evaluated by an in vitro micronucleus assay - Short communication
VL  - 56
IS  - 3-4
SP  - 403
EP  - 406
DO  - 10.1556/ABiol.56.2005.3-4.22
ER  - 

@article{
author = "Đelić, N and Potparević, Biljana and Đelić, D",
year = "2005",
abstract = "The objective of the present study was to evaluate possible genetic changes in cultured human lymphocytes treated with estradiol, using the cytokinesis block micronucleus assay. Eight experimental concentrations of estradiol were used (range from 10(-10) M to 0.7 x 10(-4) M). The obtained results indicate that estradiol exhibits aneugenic and/or clastogenic effects, expressed as increased frequency of micronucleated lymphocytes at two highest experimental concentrations used in this investigation. In addition to genotoxic effects, these concentrations decreased the cytokinesis block proliferation index (CBPI) and percentage of binucleated cells, indicating the cell cycle delay and possible cytotoxic effects. In conclusion, estradiol treatment might represent a human health risk, especially if overdosed or used for a prolonged period of time.",
publisher = "Akademiai Kiado, Budapest",
journal = "Acta Biologica Hungarica",
title = "Mutagenic activity of estradiol evaluated by an in vitro micronucleus assay - Short communication",
volume = "56",
number = "3-4",
pages = "403-406",
doi = "10.1556/ABiol.56.2005.3-4.22"
}

Đelić, N., Potparević, B.,& Đelić, D.. (2005). Mutagenic activity of estradiol evaluated by an in vitro micronucleus assay - Short communication. in Acta Biologica Hungarica
Akademiai Kiado, Budapest., 56(3-4), 403-406.
https://doi.org/10.1556/ABiol.56.2005.3-4.22

Đelić N, Potparević B, Đelić D. Mutagenic activity of estradiol evaluated by an in vitro micronucleus assay - Short communication. in Acta Biologica Hungarica. 2005;56(3-4):403-406.
doi:10.1556/ABiol.56.2005.3-4.22 .

Đelić, N, Potparević, Biljana, Đelić, D, "Mutagenic activity of estradiol evaluated by an in vitro micronucleus assay - Short communication" in Acta Biologica Hungarica, 56, no. 3-4 (2005):403-406,
https://doi.org/10.1556/ABiol.56.2005.3-4.22 . .

TY  - JOUR
AU  - Potparević, Biljana
AU  - Živković, L
AU  - Đelić, N
AU  - Bajić, Vladan
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/477
AB  - Cytogenetic analysis of the X chromosome in phytohaemagglutinin stimulated peripheral blood lymphocytes was evaluated in 12 sporadic Alzheimer disease (AD) patients and in 11 healthy subjects. For chromosome analysis two methods were used: (1) standard analysis of G-banded metaphase chromosomes and; (2) fluorescent in situ hybridization (FISH) for the detection of the X chromosome centromeric region in interphase nuclei. Cytogenetic analysis revealed that the X chromosome expresses premature centromere division (PCD) in AD females in 10.53% of metaphase cells and in 15.22% of interphase nuclei. In AD men the percentages were 3.98 and 6.06%, respectively. X chromosome PCD in the female control group showed a percentage of 7.46% in metaphase cells and 9.35% in interphase nuclei and in male controls the percentages were 2.84% in metaphases and 5.54% in interphase nuclei. The results of FISH analysis showed that PCD could occur much earlier than metaphase of mitosis, i.e. in interphase of the cell cycle, immediately after replication. The FISH method can be used for PCD verification in all phases of the cell cycle in various disorders including AD.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle
VL  - 39
IS  - 5
SP  - 849
EP  - 854
DO  - 10.1016/j.exger.2004.01.012
ER  - 

@article{
author = "Potparević, Biljana and Živković, L and Đelić, N and Bajić, Vladan",
year = "2004",
abstract = "Cytogenetic analysis of the X chromosome in phytohaemagglutinin stimulated peripheral blood lymphocytes was evaluated in 12 sporadic Alzheimer disease (AD) patients and in 11 healthy subjects. For chromosome analysis two methods were used: (1) standard analysis of G-banded metaphase chromosomes and; (2) fluorescent in situ hybridization (FISH) for the detection of the X chromosome centromeric region in interphase nuclei. Cytogenetic analysis revealed that the X chromosome expresses premature centromere division (PCD) in AD females in 10.53% of metaphase cells and in 15.22% of interphase nuclei. In AD men the percentages were 3.98 and 6.06%, respectively. X chromosome PCD in the female control group showed a percentage of 7.46% in metaphase cells and 9.35% in interphase nuclei and in male controls the percentages were 2.84% in metaphases and 5.54% in interphase nuclei. The results of FISH analysis showed that PCD could occur much earlier than metaphase of mitosis, i.e. in interphase of the cell cycle, immediately after replication. The FISH method can be used for PCD verification in all phases of the cell cycle in various disorders including AD.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle",
volume = "39",
number = "5",
pages = "849-854",
doi = "10.1016/j.exger.2004.01.012"
}

Potparević, B., Živković, L., Đelić, N.,& Bajić, V.. (2004). Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 39(5), 849-854.
https://doi.org/10.1016/j.exger.2004.01.012

Potparević B, Živković L, Đelić N, Bajić V. Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle. in Experimental Gerontology. 2004;39(5):849-854.
doi:10.1016/j.exger.2004.01.012 .

Potparević, Biljana, Živković, L, Đelić, N, Bajić, Vladan, "Analysis of premature centromere division (PCD) of the X chromosome in Alzheimer patients through the cell cycle" in Experimental Gerontology, 39, no. 5 (2004):849-854,
https://doi.org/10.1016/j.exger.2004.01.012 . .