title: Age-dependent accumulation of 8-oxoguanine in the DNA and RNA in various rat tissues.
abstract: The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.
authors.affiliation: Graduate School, Wenzhou Medical College, University Town, Wenzhou, Zhejiang 325035, China.
authors.forename: Ben
authors.initials: B
authors.lastname: Nie
authors.forename: Wei
authors.initials: W
authors.lastname: Gan
authors.forename: Fei
authors.initials: F
authors.lastname: Shi
authors.forename: Guo-Xin
authors.initials: GX
authors.lastname: Hu
authors.forename: Lian-Guo
authors.initials: LG
authors.lastname: Chen
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: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000375:Aging / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000097:blood / Q000652:urine; D006147:Guanine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism / Q000652:urine; D008297:Male; D013058:Mass Spectrometry; D009928:Organ Specificity; D010084:Oxidation-Reduction; D012313:RNA / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C024829:8-hydroxyguanine; D006147:Guanine; D012313:RNA; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine