Further evidence for a possible role of conformation in the immunogenicity and antigenicity of the oxidative DMA lesion, 8-oxo-2′deoxyguanosine
Further evidence for a possible role of conformation in the immunogenicity and antigenicity of the oxidative DMA lesion, 8-oxo-2′deoxyguanosine
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DOI：
10.3109/10715769809066883
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发表时间：
1998-01-01
影响因子：
3.3
通讯作者：
Lunec, J
中科院分区：
文献类型：
--
作者：
Cooke, MS;Herbert, KE;Lunec, J
活性氧对DNA的损伤被认为是许多病理条件中的重要因素，包括衰老和致癌作用。因此，灵敏的检测和定量的氧化DNA损伤的方法的发展一直是至关重要的。最受关注的氧化修饰的碱基产物是8-oxodeoxoguanosine（8-oxodG），它是公认的氧化DNA损伤的标志物，尽管多克隆和单克隆抗体先前都已被提高到8-oxodG，但它们在大多数情况下都未能识别DNA聚合物内的这种损伤。我们，通过稀释克隆，产生了一种单克隆抗体，似乎优先识别8-oxodG脱氧鸟苷（dG）在单链氧化修饰的DNA。当DNA是双链的时候，这种区别并不明显。以前的工作表明，8-oxodG有利于顺式糖苷构象，由于空间排斥，而dG假设反。我们目前的初步数据似乎支持的假设，这是这些差异的构象，除了结构识别的病变本身，这是负责的歧视，由我们的抗体，8-oxodG在dG的单链DNA。
Damage to DNA by reactive oxygen species is acknowledged to be an important factor in a number of pathological conditions, including ageing and carcinogenesis. As a consequence, the development of methods for the sensitive detection and quantitation of oxidative DNA lesions has been of paramount importance. The oxidatively modified base product which has achieved most attention is 8-oxodeoxyguanosine (8-oxodG) and is a recognised marker of oxidative DNA damage.Although both polyclonal and monoclonal antibodies have previously been raised to 8-oxodG these have, for the most part, failed to recognise this lesion within the DNA polymer. We have, through dilution cloning, produced a monoclonal antibody which appears to preferentially recognise 8-oxodG over deoxyguanosine (dG) in single-stranded oxidatively modified DNA. Such discrimination was not apparent when the DNA was double-stranded. Previous work has shown that 8-oxodG favours the syn glycosidic conformation due to steric repulsion, whereas dG assumes the anti. We present initial data that appear to support the postulate that it is these differences in conformation, in addition to structural recognition of the lesion itself, which are responsible for the discrimination, by our antibody, of 8-oxodG over dG in single-stranded DNA.