Age-dependent oxidative stress-induced DNA damage in Down’s lymphocytes q Marianna Zana a, * , Anita Sze ´cse ´nyi b ,A ´ gnes Czibula b , Annama ´ria Bjelik a , Anna Juha ´sz a , A ´ gnes Rimano ´czy a , Krisztina Szabo ´ c ,A ´ gnes Vetro ´ a , Pe ´ter Sz} ucs d ,A ´ gnes Va ´rkonyi e , Magdolna Pa ´ka ´ski a , Krisztina Boda f , Istva ´n Rasko ´ b , Zolta ´n Janka a , Ja ´nos Ka ´lma ´n a a Department of Psychiatry, Alzheimer’s Disease Research Center, Faculty of Medicine, Albert Szent-Gyo ¨ rgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St., Szeged, H-6725, Hungary b Biological Research Center of Hungarian Academy of Sciences, Institute of Genetics, 62 Temesva ´ ri St., Szeged, H-6726, Hungary c Department of Child and Adolescent Psychiatry, Faculty of Medicine, Albert Szent-Gyo ¨ rgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 6 Semmelweis St., Szeged, H-6725, Hungary d Children’s Medical Home, 45 Agyagos St., Szeged, H-6723, Hungary e Department of Pediatrics, Faculty of Medicine, Albert Szent-Gyo ¨ rgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 14-15 Kora ´ nyi St., Szeged, H-6720, Hungary f Department of Medical Informatics, Faculty of Medicine, Albert Szent-Gyo ¨ rgyi Center for Medical and Pharmaceutical Sciences, University of Szeged, 9 Kora ´ nyi St., Szeged, H-6720, Hungary Received 25 April 2006 Available online 5 May 2006 Abstract The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down’s syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were mea- sured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrat- ed in Alzheimer’s disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS chil- dren as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults. Ó 2006 Elsevier Inc. All rights reserved. Keywords: Down’s syndrome; Alzheimer’s disease; Oxidative stress; Lymphocyte; Comet assay; DNA repair Oxygen is necessary for life, but paradoxically, as a by-product of its metabolism, it produces reactive oxygen species (ROS), which are highly toxic to cells [1]. Oxidative stress (OS), defined as an imbalance between the generation and removal of ROS, may be a significant event in the pathogenesis of a number of neurodegenerative diseases, e.g., Alzheimer’s disease (AD) and Down’s syndrome (DS) (trisomy 21). According to the ‘‘gene dosage effect’’ hypothesis of DS [2], the reason for the increased OS is the presence of an extra copy of chromosome 21 and the consecutive overexpression of the genes located on it. The excessive amounts of the encoded proteins result in overconsumption of their substrates and exacerbated 0006-291X/$ - see front matter Ó 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.bbrc.2006.04.167 q Abbreviations: Ab, b-amyloid peptide; AD, Alzheimer’s disease; APP, amyloid precursor protein; CNS, central nervous system; CNT, control; DS, Down’s syndrome; EndoIII, endonuclease III; Fpg, formamidopyr- imidine DNA-glycosylase; H 2 O 2 , hydrogen peroxide; OS, oxidative stress; PBS, phosphate-buffered saline; ROS, reactive oxygen species; SD, standard deviation; SEM, standard error of mean; SOD-1, cytoplasmic Cu 2+ /Zn 2+ superoxide dismutase; SSB, single strand break. * Corresponding author.Fax: +36 62 545973. E-mail address: mzana@freemail.hu (M. Zana). www.elsevier.com/locate/ybbrc Biochemical and Biophysical Research Communications 345 (2006) 726–733 BBRC