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APART FROM hunches, however, it's hard to tell whether the spectrum and abundance of lesions formed in these in vitro experiments accurately reflect what's going on in the cell. Of the 50-plus lesions identified in in vitro experiments, only a dozen or so have been detected in vivo, according to Jean Cadet, scientific adviser at Commissariat à l'Energie Atomique (CEA), Grenoble, France. Cadet has been trying to measure the cellular levels of various oxidative DNA lesions for more than a decade. And this is no easy matter, he points out. A decade ago, scientists thought that tens of thousands of 8-oxoguanine lesions were present in each cell's copy of the genome at any given time, Cadet tells C&EN. But in part by making the switch from detecting 8-oxoguanine electrochemically to detecting it by more sensitive and specific mass spectrometric methods, his lab has shown that this number is actually on the order of a few hundred 8-oxoguanines. This translates into only a few 8-oxoguanines per 10 million normal bases. But even this amended number remains controversial. Cadet and his coworkers have also tried to determine the abundance of various oxidative lesions formed in leukemia cells exposed to -radiation. They found that nearly three times as much Fapy-G as 8-oxoguanine is formed under these conditions [Radiat. Res., 157, 589 (2002)]. Others, including Dizdaroglu, have found similar ratios of Fapy-G to 8-oxoguanine in vivo. "It's important to remember, however, that the most prevalent DNA lesion is not necessarily the most dangerous one to the cell," Cadet is quick to point out. |
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