Mutation Research 486 (2001) 207–216 DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser 326 /Cys 326 Kai Janssen a,b , Kirsten Schlink a , Walter Götte a , Birgit Hippler b , Bernd Kaina b,∗ , Franz Oesch a a Institute of Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany b Division of Applied Toxicology, University of Mainz, Obere Zahlbacher Strasse 67, D-55131 Mainz, Germany Received 20 February 2001; received in revised form 28 May 2001; accepted 29 May 2001 Abstract 8-Oxoguanine DNA glycosylase 1 (OGG1) is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8oxoG) from DNA. Since 8oxoG is a highly mispairing lesion, decreased OGG1 expression level could lead to a higher background mutation frequency and could possibly increase the cancer risk of an individual under oxidative stress. In order to analyse the natural variation of OGG1, we measured the DNA repair activity in human lymphocytes of healthy individuals by means of an 8oxoG-containing oligonucleotide assay. The data obtained revealed a two fold interindividual variation of OGG1 activity in lymphocytes. There was no difference in OGG1 activity due to gender and smoking behaviour. Transcriptional analyses of OGG1 showed the expression of two isoforms, 1a and b, in lymphocytes. Structural analysis of the human OGG1 (hOGG1) gene revealed a Ser 326 /Cys 326 polymorphism in the Caucasian population with allele frequencies of 75% for Ser 326 and 25% for Cys 326 . This polymorphism was not associated with altered OGG1 activity. The described routine test system for measuring OGG1 activity in cryopreserved lymphocytes provided highly reproducible results and is a useful tool for risk assessment associated with alterations in the repair of oxidative DNA damage. © 2001 Published by Elsevier Science B.V. Keywords: DNA repair; 7,8-Dihydro-8-oxoguanine; Human OGG1; Genetic polymorphism; Lymphocytes 1. Introduction Oxidative DNA damage is mediated by reactive oxygen species (ROS) including superoxide ion Abbreviations: ROS, reactive oxygen species; 8oxoG, 7,8-dihydro- 8-oxoguanine; OGG1, 8-oxoguanine DNA glycosylase 1; PAGE, polyacrylamide gelelectrophoresis; RT-PCR, reverse transcriptase- PCR; S.D., standard deviation ∗ Corresponding author. Tel.: +49-6131-393-3246; fax: +49-6131-393-3421. E-mail address: kaina@mail.uni-mainz.de (B. Kaina). (O 2 -• ), hydrogen peroxide (H 2 O 2 ) and hydroxyl radical (HO • ) as by-products of metabolism [1]. Exogenous sources of ROS are ionising radiation, free radicals, singlet oxygen sensitizer dyes and redox-active organic molecules. Irrespective of their source, ROS are capable to produce oxidative DNA damage [2,3]. DNA lesions produced by ROS are a cause for mutations that can activate oncogenes or in- activate tumour suppressor genes altering cell growth control [3,4]. 7,8-Dihydro-8-oxoguanine (8oxoG) is one of the most important lesions produced in DNA 0921-8777/01/$ – see front matter © 2001 Published by Elsevier Science B.V. PII:S0921-8777(01)00096-9