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However, as recent research is emphasizing, 8-oxoguanine is not the only player. More than 50 lesions that arise from the attack of oxygen radicals on DNA have been identified so far. "And there's no way of estimating how many we haven't found yet," notes Miral Dizdaroglu, a chemist at the National Institute of Standards & Technology. Dizdaroglu has shown that hydroxyl radicals react with all four DNA bases, both in vitro and in vivo, spawning a plethora of products. He and his coworkers at NIST are using gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry to characterize this soup of lesions. The lesions they've found to commonly form in vitro include 8-oxoguanine, 8-oxoadenine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (Fapy-G), 4,6-diamino-5-formamidopyrimidine (Fapy-A), 5-hydroxycytosine, and 5-hydroxyuracil. But the relative yields of these lesions depend on experimental conditions, he cautions. Because there's less oxygen in the nucleus than elsewhere in the cell, Dizdaroglu suspects that the soup of lesions formed with hydroxyl radicals under low oxygen conditions--which is dominated by 8-oxoguanine and Fapy-G--may paint the most accurate picture of the oxidative damage that cells have to cope with. |
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