Mutation Research 676 (2009) 1–4 Contents lists available at ScienceDirect Mutation Research/Genetic Toxicology and Environmental Mutagenesis journal homepage: www.elsevier.com/locate/gentox Community address: www.elsevier.com/locate/mutres Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in patients with type-1 diabetes mellitus Nilüfer Cinkilic a , Sinem Kiyici b , Serap Celikler a , Ozgur Vatan a , Ozen Oz Gul b , Ercan Tuncel b,∗ , Rahmi Bilaloglu a a Uludag University Science and Arts Faculty, Biology Department, Gorukle, Bursa, Turkey b Uludag University Faculty of Medicine, Department of Endocrinology and Metabolism, Gorukle, Bursa, Turkey article info Article history: Received 29 September 2008 Received in revised form 16 February 2009 Accepted 20 February 2009 Available online 5 April 2009 Keywords: Type-1 diabetes Chromosome aberrations Sister chromatid exchange Micronucleus formation abstract Oxidative stress-induced DNA damage seems to play a role in the pathogenesis of type-1 diabetes mellitus and its complications. Several in vitro assays have been used to measure the DNA damage produced by oxidative stress. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. SCE, CA and MN tests were carried out with the blood-cell cultures from 35 type-1 diabetic patients and 15 healthy, age- and sex-matched control subjects. The mean age of the type-1 diabetic patients was 31.89 ± 10.01 years, with a mean duration of the diabetes of 7.8 ± 6.02 years. The mean level of HbA1c of the type-1 diabetic patients was 8.37 ± 1.36%. Only three (8.5%) patients with type- 1 diabetes mellitus had an HbA1c level below 7%. Patients with type-1 diabetes mellitus showed a higher frequency of SCE compared with controls (5.44 ± 1.47 and 2.54 ± 0.82, respectively, p < 0.001), but there was no significant correlation between the duration of diabetes, HbA1c and SCE. No significant difference was found in CA or MN frequency in type-1 diabetic patients compared with controls. In conclusion, these results suggest that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE. Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency. © 2009 Elsevier B.V. All rights reserved. 1. Introduction Oxidative stress plays a crucial role in the cellular and molecular mechanisms of tissue injury in a wide spectrum of disease states [1]. Type-1 diabetes mellitus is a complex multifactorial disorder caused by absolute insulin deficiency due to destruction of the pancreatic -cells [2]. Pancreatic damage caused by oxidative stress has been involved in the pathogenesis of type-1 diabetes mellitus [3]. Sys- temic oxidative stress is present upon early onset of type-1 diabetes mellitus and becomes stronger over time [1]. Production of reactive oxygen species (ROS) and lipid peroxidation are increased in dia- betic patients, especially in those with poor glycemic control and hypertriglyceridemia [4]. Previous studies have clearly shown that ROS, including O 2 - , OH • , and H 2 O 2 , are highly reactive and capa- ble of damaging cellular macromolecules, including proteins, lipids and DNA [5]. During the last decades, several in vitro assays have been developed for measurement of genotoxicity. The sister chromatid ∗ Corresponding author. Tel.: +90 224 2951112; fax: +90 224 4428038. E-mail address: ercant@uludag.edu.tr (E. Tuncel). exchange (SCE) test, analysis of chromosomal aberrations (CA) and the cytokinesis-block micronucleus (CBMN) assay in lymphocytes are being used extensively to evaluate the presence and extent of chromosomal damage in human populations [6]. There are limited reports on the association between diabetes and the occurrence of genotoxic effects. Sheth et al. [7] reported that there was a signifi- cant increase in SCE frequency in type-2 diabetic patients compared with healthy controls. However, there is no knowledge about SCE, CA and micronuclei (MN) in type-1 diabetic patients. Since free radical-induced DNA damage can be measured in vitro, we sought in this study to evaluate type-1 diabetes-associated genotoxicity by use of three cytogenetic assay systems. We evaluated CA, SCE and MN in cultured lymphocytes from individuals with type-1 diabetes mellitus and compared the results with those in healthy controls. 2. Materials and methods 2.1. Subjects A total of 35 patients with type-1 diabetes mellitus and 15 age- and sex-matched healthy control subjects were studied. Patients were recruited from pre-screened type-1 diabetic patients from an endocrinology outpatient clinic of a tertiary referral center. Type-1 diabetes mellitus was clinically defined as a diagnosis made prior to age 30, with a continuous need for insulin therapy within one year of diagnosis 1383-5718/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.mrgentox.2009.02.014