%0 Journal Article
%T DNA Damage in Rheumatoid Arthritis: An Age-Dependent Increase in the Lipid Peroxidation-Derived DNA Adduct, Heptanone-Etheno-2¡ä-Deoxycytidine
%A Masako Ogawa
%A Tomonari Matsuda
%A Atsushi Ogata
%A Toshimitsu Hamasaki
%A Atsushi Kumanogoh
%A Toshihiko Toyofuku
%A Toshio Tanaka
%J Autoimmune Diseases
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/183487
%X Objective. To evaluate what types of DNA damages are detected in rheumatoid arthritis (RA). Methods. The DNA adducts such as 8-oxo-hydroxy-7,8-dihydro-2¡ä-deoxyguanosine (8-oxo-dG), 1,N6-etheno-2¡ä-deoxyadenosine (¦ÅdA), and heptanone-etheno-2¡ä-deoxycytidine (H¦ÅdC) in genomic DNAs, derived from whole blood cells from 46 RA patients and 31 healthy controls, were analyzed by high-performance liquid chromatography tandem mass spectrometry, and their levels in RA patients and controls were compared. In addition, correlation between DNA adducts and clinical parameters of RA was analyzed. Results. Compared with controls, the levels of H¦ÅdC in RA were significantly higher ( ) and age dependent (r = 0.43, P < 0.01), while there was no significant difference in 8-oxo-dG and ¦ÅdA accumulation between RA patients and controls. H¦ÅdC levels correlated well with the number of swollen joints (r = 0.57, P < 0.0001) and weakly with the number of tender joints (r = 0.26, P = 0.08) of RA patients, while they did not show a significant association with serological markers such as C-reactive protein and matrix metalloproteinase 3. Conclusion. These findings indicate that H¦ÅdC may have some influence on the development of RA and/or its complications. 1. Introduction Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease of the joints and surrounding tissues, accompanied by intense pain, irreversible joint destruction, and systemic complications [1]. Its etiology has not been fully clarified yet, but oxidative stress is one of the pathological factors, which contribute to its development [2¨C5]. Shao et al. recently reported detecting the presence of DNA damage and deficiency of the DNA repair enzyme, ataxia telangiectasia mutated (ATM), in RA T cells [6]. Moreover, a DNA oxidation product, 8-oxo-hydroxy-7,8-dihydro-2¡ä-deoxyguanosine (8-oxo-dG), has been shown to be highly expressed in RA patients [2]. DNA damage induced by exposure to ionizing radiation, ultraviolet light, and exogenous or endogenous chemical mutagens causes DNA strand breakages, which are thought to be mutagenic, carcinogenic, and aging factors [2]. Additionally as new DNA damage, lipid peroxidation-derived DNA adducts have been recently reported in human [7], and lipid peroxidation has been also considered as a factor of the pathogenesis or the local inflammatory response of RA [4, 8¨C10]. Representative DNA adducts are 8-oxo-dG, 1,N6-etheno-2¡ä-deoxyadenosine (¦ÅdA), and heptanone-etheno-2¡ä-deoxycytidine (H¦ÅdC); the latter two of which are direct reactive oxygen species- (ROS-) derived and lipid
%U http://www.hindawi.com/journals/ad/2013/183487/