title: Age-dependent increases in the oxidative damage of DNA, RNA, and their metabolites in normal and senescence-accelerated mice analyzed by LC-MS/MS: urinary 8-oxoguanosine as a novel biomarker of aging.
abstract: A sensitive and accurate isotope-diluted LC-MS/MS method was developed for determination of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn), derived from DNA, and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn), derived from RNA, in various tissue specimens obtained from normal SAMR1 and senescence-accelerated SAMP8 mice. An age-dependent accumulation of oxidative DNA and RNA damage was observed in all the organs examined, namely, the brain, liver, lungs, heart, kidneys, and testes. Among these, the brain samples exhibited the highest values for DNA damage. These age-related increases in the 8-oxoguanine content in DNA and RNA occurred more rapidly in SAMP8 than in SAMR1 mice. Age-related increases in the contents of 8-oxo-dGsn and 8-oxo-Gsn were also observed in the plasma and urine; however, the ratios of 8-oxo-Gsn to 8-oxo-dGsn in these samples were considerably higher (6 to 13) compared with the values for the samples derived from other tissues (roughly 1), indicating that measurement of 8-oxo-Gsn in urine could be a novel means of evaluating the aging process.
authors.affiliation: Graduate School, Chinese Academy of Medical Sciences and Peking Union Medical College, Dongdan, Beijing 100730, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gan
authors.forename: Ben
authors.initials: B
authors.lastname: Nie
authors.forename: Fei
authors.initials: F
authors.lastname: Shi
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Xu
authors.forename: Jian-Chang
authors.initials: JC
authors.lastname: Qian
authors.forename: Yasumitsu
authors.initials: Y
authors.lastname: Takagi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Sekiguchi
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Cai
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013737:Testis / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006151:Guanosine; C046215:8-hydroxyguanosine; D012313:RNA; D004247:DNA