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    Evaluation of chromosomal DNA damage, cytotoxicity, cytostasis, oxidative DNA damage and their relationship with endocrine hormones in patients with acute organophosphate poisoning
    (Elsevier Science Bv, 2018) Gündoğan, Kürşat; Dönmez Altuntaş, Hamiyet; Hamurcu, Zuhal; Akbudak, Ismail Hakkı; Sungur, Murat; Bitgen, Nazmiye; Başkol, Gülden; Bayram, Fahri
    Pesticides are commonly used compounds in agriculture. Especially, organophosphates (OPs) are among the extensively used pesticides. Therefore, OPs poisoning is common, especially in underdeveloped and developing countries. Primary aim of this study was to research the effects of acute OPs poisoning on genome instability in the individuals' lymphocytes with acute OPs poisoning both by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay to examine chromosome/genome damage, cell proliferation index and cell death rate and by using the plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels to determine oxidative DNA damage. Secondary aim of this study was also to assess whether a relation exists between endocrine hormones and the genome damage in acute OPs poisoning. In the study, blood samples were analysed of 13 patients before and after treatment admitted to the Department of Intensive Care Unit with acute OPs poisoning and of 13 healthy subjects of similar age and sex. The present study demonstrates that genome damage (micronucleus; MN and nucleoplasmic bridges; NPBs frequencies), apoptotic and necrotic cell frequencies increased in lymphocytes of patients with acute OPs poisoning before treatment and decreased after treatment. The present study also show that CBMN cyt assay parameters and 8-OHdG levels could be affected by some endocrine hormones such as E2, fT3, fT4, GH, IGF-1, FSH, LH, TSH, PRL, but not be related to ACTH and tT levels in acute OPs poisoning. In conclusion, it is believed that this is the first study to evaluate the chromosomal/oxidative DNA damage, cell proliferation, cell death and their associations with endocrine hormones in acute OPs poisoning. These preliminary findings need to be supported by further studies with larger sample sizes.
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    Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer
    (Hindawi Publishing Corporation, 2017) Dönmez-Altuntaş, Hamiyet; Bayram, Fahri; Bitgen, Nazmiye; Ata, Sibel; Hamurcu, Zuhal; Başkol, Gülden
    Thyroid nodules are a common clinical problem worldwide. Although thyroid cancer accounts for a small percentage of thyroid nodules, the majority are benign. 8-Hydroxy-2 '-deoxyguanosine (8-OHdG) levels are a marker of oxidative stress and play a key role in the initiation and development of a range of diseases and cancer types. This study evaluates cytokinesis-block micronucleus cytome (CBMN-cyt) assay parameters and plasma 8-OHdG levels and their association with thyroid nodule size and thyroid hormones in patients with multinodular goiter. The study included 32 patients with multinodular goiter and 18 age-and sex-matched healthy controls. CBMN-cyt assay parameters in peripheral blood lymphocytes of patients with multinodular goiter and controls were evaluated, and plasma 8-OHdG levels were measured. The micronucleus (MN) frequency (chromosomal DNA damage), apoptotic and necrotic cells (cytotoxicity), and plasma 8-OHdG levels (oxidative DNA damage) were significantly higher among patients with multinodular goiter. Our study is the first report of increased chromosomal and oxidative DNA damage in patients with multinodular goiter, which may predict an increased risk of thyroid cancer in these patients. MN frequency and plasma 8-OHdG levels may be markers of the carcinogenic potential of multinodular goiters and could be used for early detection of different cancer types, including thyroid cancer.
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    Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma
    (Taylor & Francis, 2016) Bitgen, Nazmiye; Dönmez-Altuntaş, H.; Bayram, F.; ÇakIr, I.; Hamurcu, Z.; Diri, H.; Başkol, G.; Şenol, S.; Durak, A. C.
    Prolactinoma is the most common pituitary tumor. Most pituitary tumors are benign, but they often are clinically significant. We investigated cytokinesis-block micronucleus cytome (CBMN cyt) assay parameters and oxidative DNA damage in patients with prolactinoma to assess the relations among age, prolactin level, pituitary adenoma diameter and 8-hydroxy-2'-deoxyguanosine (8-OHdG) level in patients with prolactinoma. We investigated 27 patients diagnosed with prolactinoma and 20 age- and sex-matched healthy controls. We measured CBMN cyt parameters and plasma 8-OHdG levels in peripheral blood lymphocytes of patients with prolactinoma and controls. The frequencies of micronucleus (MN), nucleoplasmic bridge, nuclear bud, apoptotic and necrotic cells, and plasma 8-OHdG levels in patients with prolactinoma were significantly greater than controls. MN frequency was correlated positively with age, prolactin levels and pituitary adenoma diameters in patients with prolactinoma. The increased chromosomal and oxidative DNA damage, and the positive correlation between MN frequency, prolactin levels and pituitary adenoma diameters may be associated with increased risk of cancer in patients with prolactinoma, because increased MN frequency is a predictor of cancer risk.
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    Unexpected relationship of extracellular ATP with intracellular Ca concentration in hepG2 cells
    (SUAMTHI PUBLICATIONS, 2019) Caner, Armağan; Bitgen, Nazmiye; Önal, Müge Gülcihan
    The aim of our study is to examine the effect of exfracellular ATP whether it is correlated with intracellular Ca concentrations ([Ca2+]i) on human liver hepatocellular cells (HepG2). The exfracellular ATP is responsible for regulating both cells signaling and cell functions. ATP maintains these effects through purinergic P2 receptors. The extracellular ATP promotes the release of Ca2+ from the Ca2+ stores to the cytoplasm in the cell and increases [Ca2+] I in the cell. In our study, various concentrations of ATP (10(-3)M-10(-7)M) were applied to HepG2 cells and incubated for 24 hours, 48 hours, and 72 hours. At these concentrations, the proliferation of cells and apoptosis of the cells was examined for 24 hours, 48 hours, and 72 hours. Similarly, cells with different ATP concentrations incubated for 24 hours and 48 hours were loaded with Indo 1FF AM calcium indicator to measure [Ca2+]i. Surprising results were obtained, 10(-6)M-10(-7)M exfracellular ATP was found to be more toxic than 10(-3) M-10(-4) extracellular ATP, (p<0.05). Low concentrations ofATP also reduced [Ca2+]i for 24 hours and 48 hours of incubations (p<0.01). As a result, low concentration exfracellular ATP is more toxic in HepG2 cells. At the same time, the exfracellular ATP correlates with [Ca2+]i.