8-Hydroxyadenine (BioDeep_00000025560)

描述信息

8-hydroxyadenine is an intermediate in the oxidation of adenine to 2,8-dihydroxyadenine by xanthine oxidase (EC 1.1.3.22). A controversy exists as to whether or not this metabolite is a marker of DNA damage. Several papers have reported an artifactual formation of a number of modified bases from intact DNA bases during derivatization of DNA hydrolysates to be analyzed by gas chromatography-mass spectrometry (GC/MS). These reports dealt with 8-hydroxyadenine (8-OH). It needs to be emphasized that the procedures for hydrolysis of DNA and derivatization of DNA hydrolysates used in these papers substantially differed from the established procedures previously described. Furthermore, a large number of relevant papers reporting the levels of these modified bases in DNA of various sources have been ignored. Interestingly, the levels of modified bases reported in the literature were not as high as those reported prior to prepurification. Levels of 8-OH-Ade were quite close to, or even the same as, or smaller than the level reported after prepurification. All these facts raise the question of the validity of the claims about the measurement of these modified DNA bases by GC/MS. Oxidative damage to DNA may play an important role in aging and neurodegenerative diseases such as Alzheimers disease (AD). Attack on DNA by reactive oxygen species, particularly hydroxyl radicals, can lead to strand breaks, DNA-DNA and DNA-protein cross-linking, sister chromatid exchange and translocation, and formation of at least 20 oxidized base adducts. Modification of DNA bases can lead to mutation and altered protein synthesis. In late-stage AD brain, several studies have shown an elevation of the base adducts 8-hydroxyadenine (8-OHA). Several studies have shown a decline in repair of 8-OHG in AD. Most recently studies have shown elevated 8-OHA in nuclear and mitochondrial DNA in mild cognitive impairment, the earliest detectable form of AD, suggesting that oxidative damage to DNA is an early event in AD and not a secondary phenomenon. (PMID: 10098459, 17034348) [HMDB]
8-hydroxyadenine is an intermediate in the oxidation of adenine to 2,8-dihydroxyadenine by xanthine oxidase (EC 1.1.3.22). A controversy exists as to whether or not this metabolite is a marker of DNA damage. Several papers have reported an artifactual formation of a number of modified bases from intact DNA bases during derivatization of DNA hydrolysates to be analyzed by gas chromatography-mass spectrometry (GC/MS). These reports dealt with 8-hydroxyadenine (8-OH). It needs to be emphasized that the procedures for hydrolysis of DNA and derivatization of DNA hydrolysates used in these papers substantially differed from the established procedures previously described. Furthermore, a large number of relevant papers reporting the levels of these modified bases in DNA of various sources have been ignored. Interestingly, the levels of modified bases reported in the literature were not as high as those reported prior to prepurification. Levels of 8-OH-Ade were quite close to, or even the same as, or smaller than the level reported after prepurification. All these facts raise the question of the validity of the claims about the measurement of these modified DNA bases by GC/MS. Oxidative damage to DNA may play an important role in aging and neurodegenerative diseases such as Alzheimers disease (AD). Attack on DNA by reactive oxygen species, particularly hydroxyl radicals, can lead to strand breaks, DNA-DNA and DNA-protein cross-linking, sister chromatid exchange and translocation, and formation of at least 20 oxidized base adducts. Modification of DNA bases can lead to mutation and altered protein synthesis. In late-stage AD brain, several studies have shown an elevation of the base adducts 8-hydroxyadenine (8-OHA). Several studies have shown a decline in repair of 8-OHG in AD. Most recently studies have shown elevated 8-OHA in nuclear and mitochondrial DNA in mild cognitive impairment, the earliest detectable form of AD, suggesting that oxidative damage to DNA is an early event in AD and not a secondary phenomenon. (PMID: 10098459, 17034348).

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