Chromosomal and oxidative DNA damage in non-functioning pituitary adenomas
Abstract
Introduction: Clinically non-functioning pituitary adenomas (NFPA) are common tumours of the pituitary gland and are mainly considered as benign. The primary aim of this study was to research the effects of NFPA on genome instability in patients with non-functioning pituitary adenoma by using the cytokinesis-block micronucleus cytome (CBMN-cyt) assay and 8-hydroxy- 2’-deoxyguanosine (8-OHdG) assay. The second objective of this study was to assess whether there is a relationship between age, pituitary adenoma diameters, 8-OHDG levels, CBMN site assay parameters, and tumour aggressiveness.
Material and methods: The study was performed on 30 patients who had been diagnosed with NFPA and were admitted to the Department of Endocrinology and Metabolism, and 20 healthy subjects of similar age and sex.
Results: Micronucleus (MN), nucleoplasmic bridges (NPBs), nuclear bud (NBUD) frequencies, and apoptotic and necrotic cell frequencies in patients with NFPA were found to be significantly higher than in control subjects, and plasma 8-OHdG levels in patients with NFPA were statistically significantly lower than control subjects in this study.
Conclusions: It is believed that this is the first study to evaluate the aggressiveness of tumour with chromosome/oxidative DNA damage in patients with NFPA. However, further studies are needed in order to understand the cause of NFPA aggression and to evaluate these patients in terms of risk of cancer.
Keywords: 8-OHdG levelsDNA damagemicronucleusnon-functioning pituitary adenoma
References
- Zhan X, Wang X, Long Y, et al. Heterogeneity analysis of the proteomes in clinically nonfunctional pituitary adenomas. BMC Med Genomics. 2014; 7: 69.
- Zhan X, Long Y. Exploration of Molecular Network Variations in Different Subtypes of Human Non-functional Pituitary Adenomas. Front Endocrinol (Lausanne). 2016; 7: 13.
- Wang X, Guo T, Peng F, et al. Proteomic and functional profiles of a follicle-stimulating hormone positive human nonfunctional pituitary adenoma. Electrophoresis. 2015; 36(11-12): 1289–1304.
- Karppinen A, Kivipelto L, Vehkavaara S, et al. Transition From Microscopic to Endoscopic Transsphenoidal Surgery for Nonfunctional Pituitary Adenomas. World Neurosurg. 2015; 84(1): 48–57.
- Liu X, Ma S, Dai C, et al. Antiproliferative, antiinvasive, and proapoptotic activity of folate receptor α-targeted liposomal doxorubicin in nonfunctional pituitary adenoma cells. Endocrinology. 2013; 154(4): 1414–1423.
- Chanson P, Raverot G, Castinetti F, et al. French Endocrinology Society non-functioning pituitary adenoma work-group. Management of clinically non-functioning pituitary adenoma. Ann Endocrinol (Paris). 2015; 76(3): 239–247.
- Pawlikowski M, Kunert-Radek J, Radek M. Plurihormonality of pituitary adenomas in light of immunohistochemical studies. Endokrynol Pol. 2010; 61(1): 63–66.
- Yu Z, Kholova DS, Urmanova YM, et al. Reproductive Function in patients with non-functioning pituitary adenoma according to the register of the republic of Uzbekistan. Int J Biomed. 2016; 6: 133–135.
- Raappana A, Koivukangas J, Ebeling T, et al. Incidence of pituitary adenomas in Northern Finland in 1992-2007. J Clin Endocrinol Metab. 2010; 95(9): 4268–4275.
- Daly AF, Rixhon M, Adam C, et al. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006; 91(12): 4769–4775.
- Fernandez A, Karavitaki N, Wass JAH. Prevalence of pituitary adenomas: a community-based, cross-sectional study in Banbury (Oxfordshire, UK). Clin Endocrinol (Oxf). 2010; 72(3): 377–382.
- Colao A, Di Somma C, Pivonello R, et al. Hormone levels and tumour size response to quinagolide and cabergoline in patients with prolactin-secreting and clinically non-functioning pituitary adenomas: predictive value of pituitary scintigraphy with 123I-methoxybenzamide. Clin Endocrinol (Oxf). 2000; 52(4): 437–445.
- Ferrante E, Ferraroni M, Castrignanò T, et al. Non-functioning pituitary adenoma database: a useful resource to improve the clinical management of pituitary tumors. Eur J Endocrinol. 2006; 155(6): 823–829.
- Jaffe CA. Clinically non-functioning pituitary adenoma. Pituitary. 2006; 9(4): 317–321.
- Neto LV, Boguszewski CL, Araújo LA, et al. A review on the diagnosis and treatment of patients with clinically nonfunctioning pituitary adenoma by the Neuroendocrinology Department of the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab. 2016; 60(4): 374–390.
- Chanson P, Brochier S. Non-functioning pituitary adenomas. J Endocrinol Invest. 2005; 28(11 Suppl International): 93–99.
- Fenech M, Crott J, Turner J, et al. Necrosis, apoptosis, cytostasis and DNA damage in human lymphocytes measured simultaneously within the cytokinesis-block micronucleus assay: description of the method and results for hydrogen peroxide. Mutagenesis. 1999; 14(6): 605–612.
- Fenech M. Cytokinesis-block micronucleus cytome assay. Nat Protoc. 2007; 2(5): 1084–1104.
- Fenech M, Holland N, Zeiger E, et al. The HUMN and HUMNxL international collaboration projects on human micronucleus assays in lymphocytes and buccal cells — past, present and future. Mutagenesis. 2011; 26(1): 239–245.
- Thomas P, Fenech M. Cytokinesis-block micronucleus cytome assay in lymphocytes. Methods Mol Biol. 2011; 682(1): 217–234.
- Floyd R. The role of 8-hydroxyguanine in carcinogenesis. Carcinogenesis. 1990; 11(9): 1447–1450.
- Chen HI, Liou SH, Ho SF, et al. Oxidative DNA damage estimated by plasma 8-hydroxydeoxyguanosine (8-OHdG): influence of 4, 4'-methylenebis (2-chloroaniline) exposure and smoking. J Occup Health. 2007; 49(5): 389–398.
- Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009; 27(2): 120–139.
- Bitgen N, Donmez-Altuntas H, Bayram F, et al. Increased micronucleus, nucleoplasmic bridge, nuclear bud frequency and oxidative DNA damage associated with prolactin levels and pituitary adenoma diameters in patients with prolactinoma. Biotech Histochem. 2016; 91(2): 128–136.
- Bayram F, Bitgen N, Donmez-Altuntas H, et al. Increased genome instability and oxidative DNA damage and their association with IGF-1 levels in patients with active acromegaly. Growth Horm IGF Res. 2014; 24(1): 29–34.
- Hamurcu Z, Cakir I, Donmez-Altuntas H, et al. Micronucleus evaluation in mitogen-stimulated lymphocytes of patients with acromegaly. Metabolism. 2011; 60(11): 1620–1626.
- Donmez-Altuntas H, Bayram F, Bitgen N, et al. Increased Chromosomal and Oxidative DNA Damage in Patients with Multinodular Goiter and Their Association with Cancer. Int J Endocrinol. 2017; 2017: 2907281.
- Fenech M. The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations. Mutat Res. 1993; 285(1): 35–44.
- Donmez-Altuntas H, Bitgen N. Evaluation of the genotoxicity and cytotoxicity in the general population in Turkey by use of the cytokinesis-block micronucleus cytome assay. Mutat Res. 2012; 748(1-2): 1–7.
- Eastmond DA, Tucker JD. Identification of aneuploidy-inducing agents using cytokinesis-blocked human lymphocytes and an antikinetochore antibody. Environ Mol Mutagen. 1989; 13(1): 34–43.
- Olsson DS, Nilsson AG, Bryngelsson IL, et al. Excess Mortality in Women and Young Adults With Nonfunctioning Pituitary Adenoma: A Swedish Nationwide Study. J Clin Endocrinol Metab. 2015; 100(7): 2651–2658.
- Greenman Y, Stern N, Greenman Y, et al. Non-functioning pituitary adenomas. Best Pract Res Clin Endocrinol Metab. 2009; 23(5): 625–638.
- Zhan X, Desiderio DM. The use of variations in proteomes to predict, prevent, and personalize treatment for clinically nonfunctional pituitary adenomas. EPMA J. 2010; 1(3): 439–459.
- Grech G, Zhan X, Yoo BC, et al. EPMA position paper in cancer: current overview and future perspectives. EPMA J. 2015; 6(1): 9.
- Hu R, Wang X, Zhan X. Multi-parameter systematic strategies for predictive, preventive and personalised medicine in cancer. EPMA J. 2013; 4(1): 2.
- Hood L, Tian Q. Systems approaches to biology and disease enable translational systems medicine. Genom Proteom Bioinf. 2012; 10(4): 181–185.
- Bonassi S, Znaor A, Ceppi M, et al. An increased micronucleus frequency in peripheral blood lymphocytes predicts the risk of cancer in humans. Carcinogenesis. 2007; 28(3): 625–631.
- Chatzellis E, Alexandraki KI, Androulakis II, et al. Aggressive pituitary tumors. Neuroendocrinology. 2015; 101(2): 87–104.
- Pack SD, Qin LX, Pak E, et al. Common genetic changes in hereditary and sporadic pituitary adenomas detected by comparative genomic hybridization. Genes Chromosomes Cancer. 2005; 43(1): 72–82.
- Pack SD, Kirschner LS, Pak E, et al. Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex). J Clin Endocrinol Metab. 2000; 85(10): 3860–3865.
- Weil RJ, Vortmeyer AO, Huang S, et al. 11q13 allelic loss in pituitary tumors in patients with multiple endocrine neoplasia syndrome type 1. Clin Cancer Res. 1998; 4(7): 1673–1678.
- Wierinckx A, Roche M, Raverot G, et al. Integrated genomic profiling identifies loss of chromosome 11p impacting transcriptomic activity in aggressive pituitary PRL tumors. Brain Pathol. 2011; 21(5): 533–543.
- Lüdecke DK, Beck-Bornholdt HP, Saeger W, et al. Tumour ploidy in DNA histograms of pituitary adenomas. Acta Neurochir (Wien). 1985; 76(1-2): 18–22.
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