Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly
Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly
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DOI：
10.1016/j.ghir.2013.12.002
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发表时间：
2014-02-01
影响因子：
1.4
通讯作者：
Baskol, Gulden
中科院分区：
文献类型：
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作者：
Bayram, Fahri;Bitgen, Nazmiye;Baskol, Gulden
目的：本研究的目的是评估活动性肢端肥大症患者和对照组的细胞动力学阻断微核细胞组（CBMN Cyt）测定参数和氧化DNA损伤，并评估活动性肢端肥大症患者的年龄、血清胰岛素样生长因子1 （IGF-1）水平、垂体腺瘤直径、8-羟基-2 '-脱氧鸟苷（8-OHdG）水平和CBMN Cyt测定参数之间的关系。设计：研究人群包括30例活动性肢端肥大症患者和30例年龄和性别匹配的健康对照。评估活动性肢端肥大症患者和对照组外周血淋巴细胞CBMN Cyt测定参数，测定血浆8-OHdG水平。结果：肢端肥大症患者淋巴细胞微核（MN）、核质桥（NPBs）和核芽（NBUDs）频率显著高于对照组（p < 0.001、p < 0.001、p < 0.001）。肢端肥大症患者淋巴细胞凋亡和坏死细胞的频率明显高于对照组（p < 0.001和p < 0.001）。患者与对照组中期细胞数、双核细胞数（M2）、三核细胞数（M3）、四核细胞数（M4）及核分裂指数（NDI）值比较，差异均无统计学意义（p < 0.05）。肢端肥大症患者血浆8-OHdG （ng/ml）水平显著高于对照组（p < 0.005）。肢端肥大症患者淋巴细胞MN频率随血清IGF-1水平升高而升高（p < 0.05）， NPBs数量和凋亡细胞频率随血清IGF-1水平升高而降低（p < 0.01和p < 0.05）。结论：染色体/氧化DNA损伤的增加以及MN频率和血清IGF-1水平之间的正相关可能预测肢端肥大症患者恶性肿瘤的风险增加。有必要对肢端肥大症患者进行长期随访，以确定该人群的癌症风险程度。(C) 2013 Elsevier Ltd.版权所有。
Objective: The objectives of this study were to assess cytokinesis-block micronucleus cytome (CBMN Cyt) assay parameters and also oxidative DNA damage in patients with active acromegaly and controls and to assess the relationship between age, serum insulin-like growth factor 1 (IGF-1) levels, pituitary adenoma diameters, 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels and CBMN Cyt assay parameters in patients with active acromegaly.Design: The study population included 30 patients with active acromegaly and 30 age- and sex-matched healthy controls. CBMN Cyt assay parameters in peripheral blood lymphocytes of patients with active acromegaly and controls were evaluated and plasma 8-OHdG levels were measured.Results: Frequencies of micronucleus (MN), nucleoplasmic bridges (NPBs) and nuclear buds (NBUDs) in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p < 0.001, p < 0.001, p < 0.001, respectively). The frequencies of apoptotic and necrotic cells in lymphocytes of patients with acromegaly were found to be significantly higher than those in controls (p < 0.001 and p < 0.001 respectively). No statistically significant differences in the number of cells in metaphase, the number of bi-nucleated cells (M2), the number of tri-nucleated cells (M3), the number of tetra-nucleated cells (M4) and nuclear division index (NDI) values were observed between patients and controls (p > 0.05). Plasma 8-OHdG (ng/ml) levels in patients with acromegaly were found to be significantly higher than those in controls (p < 0.005). MN frequency in the lymphocytes of patients with acromegaly increased with elevated serum IGF-1 levels (p < 0.05), whereas the number of NPBs and the frequency of apoptotic cells decreased with elevated serum IGF-1 levels (p < 0.01 and p < 0.05 respectively).Conclusions: Both the increase in chromosomal/oxidative DNA damage and the positive association between MN frequency and serum IGF-1 levels may predict an increased risk of malignancy in acromegalic patients. Long-term follow-up of patients with acromegaly will be necessary to establish the degree of cancer risk in this population. (C) 2013 Elsevier Ltd. All rights reserved.