Chromosomal radiosensitivity in patients with multiple sclerosis

Milenkova, Maria; Milanov, Ivan; Kmetska, K.; Deleva, Sofia; Popova, Ljubomira; Hadjidekova, Valeria; Groudeva, Violeta; Hadjidekova, Savina; Domı́nguez, I.

doi:10.1016/j.mrfmmm.2013.08.004

Cited by 6 publications

(5 citation statements)

References 25 publications

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“…Furthermore, evidences have suggested that impaired DNA repair might also play a fundamental role in the development of agerelated neurodegenerative diseases such as amyotrophic lateral sclerosis and Huntington's disease (Coppedè and Migliore 2010). Regarding the low genetic damage in lymphocytes, same result was found by Milenkova et al (Milenkova et al 2013) in patients with RRMS (treated with immunomodulators) and SPMS (not treated with immunomodulators).…”

Section: Discussionsupporting

confidence: 83%

Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

et al. 2019

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The etiology of multiple sclerosis (MS) is still not known, but the interaction of genetic, immunological, and environmental factors seem to be involved. This study aimed to investigate genetic alterations and the vitamin D status in patients with relapsingremitting MS (RRMS) and secondary progressive MS (SPMS). A total of 53 patients (29 RRMS; 24 SPMS) and 25 healthy subjects were recruited to evaluate the micronucleated cell (MNC) frequency and nuclear abnormalities in the buccal mucosa, gene expression profiling in mononuclear cells, and plasmatic vitamin D concentration in the blood. Results showed a higher frequency of cells with karyorrhexis (SPMS) and lower frequencies of nuclear pyknosis (RRMS and SPMS) and karyolysis (SPMS) in patients with MS. Significant increase in the frequency of MNC was detected in the buccal mucosa of RRMS and SPMS patients. HIF1A, IL13, IL18, MYC, and TNF were differentially expressed in MS patients, and APP was overexpressed in cells of RRMS compared to SPMS patients. No relationship was observed between vitamin D level and the differentially expressed genes. In conclusion, the cytogenetic alterations in the buccal mucosa can be important indicators of genetic instability and degenerative processes in patients with MS. Furthermore, our data introduced novel biomarkers associated with the molecular pathogenesis of MS.

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Section: Discussionsupporting

confidence: 83%

Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

et al. 2019

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“…Similarly, elevated MN frequency has been reported in patients with cancer [28], rheumatoid arthritis [29], autoimmune diseases [30], and premature aging syndrome [31]. The presence of MN in a cell is an indicator of DNA damage and genetic instability, and it could be associated with the collateral complications in these patients and with future risk of cancer development in humans.…”

Section: Periodontitis and Oxs: Nuclear And Oxidative Dna Damagementioning

confidence: 85%

Periodontal Disease and Nuclear and Oxidative DNA Damage

Zamora‐Pérez¹,

Zúñiga‐González²,

Gómez‐Meda³

et al. 2017

Insights Into Various Aspects of Oral Health

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Oral health is an important aspect of the overall health status of an individual. DNA damage has been associated with oral health and dental factors due to the increased of oxidative stress (OxS). DNA damage can produce a wide range of effects on human health. These effects could appear immediately, but others do not become evident much later. Chronic diseases have been study to understand their mechanisms, clinical implications, and the development of secondary disease such as cancer. Periodontitis is one of the most common oral diseases. It is an inflammatory chronic infectious disease, which is characterized by the loss of supporting tissues and tooth loss caused by periodontopathogens and long-term release of reactive oxygen species (ROS); thus, oxidative stress is increased during periodontitis. Oxidative stress can produce DNA damage, including the oxidation of nucleosides, which could cause DNA strand break. This oxidative damage leads the formation of micronuclei (MN) a marker of nuclear damage. Also, oxidative stress increased 8-hydroxy-2′-deoxyguanosine levels which are the most common stable product of oxidative DNA damage.

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“…Four types of MS have been characterized: relapsing-remitting (RRMS), secondary progressive (SPMS), primary progressive (PPMS), and progressive relapsing (PRMS). The RRMS form is present in 85% of patients at disease onset, but later during the course most of them will develop the SPMS form [ 24 ]. We found two studies about MN in MS patients; they were performed to evaluate the resistance to radiation of lymphocytes from MS patients; resistance to radiation is defined as the capacity of lymphocytes to prevent the formation of MN after radiation.…”

Section: Resultsmentioning

confidence: 99%

“…When patients and healthy subjects were analyzed before and after irradiation the induction of MN was evident, although frequencies tended to be higher in healthy subjects after radiation; this fact could be the consequence of a defective proliferation rate in patients with MS or can be the reflection of MS therapies that render CD4+ T cells resistant to MN formation after radiation when compared to cells derived from healthy subjects. Lately in 2013, Milenkova et al [ 24 ] reported that immunomodulatory therapy with IFN- β or glatiramer acetate in RRMS patients reduces the number of MN in binucleated cells induced by in vitro γ -irradiation. This data suggests that the resistance to radiation by T lymphocytes in MS patients is mainly due to treatment with immunomodulatory agents.…”

Section: Resultsmentioning

confidence: 99%

“…This data suggests that the resistance to radiation by T lymphocytes in MS patients is mainly due to treatment with immunomodulatory agents. The characterization of particular sets of cells derived from MS patients is needed to further clarify their cytophatic effects, since lymphocytes in MS and actually in any AD have different characteristics that may influence cellular responses, such as higher number of cells with the Th1 profile with increased production of proinflammatory cytokines, impaired apoptotic deletion (increased production of proliferative cytokines and growth factors, such as IL-2 and upregulation of survivin), and modified T helper/T suppressor ratio [ 24 ]. Finally the mechanism of action of IFN- β is downregulation of vascular endothelial cells, decreasing the production of adhesion molecules and metalloproteases which influences migration of T cells, and inhibition of the generation of proinflammatory cytokines (TNF- α , IFN- γ , and IL-12).…”

Section: Resultsmentioning

confidence: 99%

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Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

Torres-Bugarı́n

Macriz-Romero

Ibarra

et al. 2015

BioMed Research International

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Autoimmune diseases (AD) are classified into organ-specific, systemic, and mixed; all forms of AD share a high risk for cancer development. In AD a destructive immune response induced by autoreactive lymphocytes is started and continues with the production of autoantibodies against different targets; furthermore apoptosis failure and loss of balance in oxidative stress as a consequence of local or systemic inflammation are common features seen in AD as well. Micronucleus (MN) assay can be performed in order to evaluate loss of genetic material in a clear, accurate, fast, simple, and minimally invasive test. The MN formation in the cytoplasm of cells that have undergone proliferation is a consequence of DNA fragmentation during mitosis and the appearance of small additional nuclei during interphase. The MN test, widely accepted for in vitro and in vivo genotoxicity research, provides a sensitive marker of genomic damage associated to diverse conditions. In here, we present a review of our work and other published papers concerning genotoxic effect in AD, identified by means of the MN assay, with the aim of proposing this tool as a possible early biomarker for genotoxic damage, which is a consequence of disease progression. Additionally this biomarker could be used for follow-up, to asses genome damage associated to therapies.

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Chromosomal radiosensitivity in patients with multiple sclerosis

Cited by 6 publications

References 25 publications

Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

Genetic Alterations in Patients with Two Clinical Phenotypes of Multiple Sclerosis

Periodontal Disease and Nuclear and Oxidative DNA Damage

Genotoxic Effect in Autoimmune Diseases Evaluated by the Micronucleus Test Assay: Our Experience and Literature Review

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