TOXI 134 |
| 7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) is the most studied oxidized base in DNA and may play key roles in oxidative mutagenesis and carcinogenesis in humans. There are two possible pathways to generate 8-oxodG in DNA, i.e., salvage through 8-oxo-dGTP and direct oxidation of guanine in DNA. Demonstration of the former pathway has been hampered because of insufficiently sensitive analytical methods to measure the 8-oxodG. We developed a method to measure 8-oxodG in media, cells and DNA using accelerator mass spectrometer (AMS) and demonstrated that substantial part of 8-oxodG in the medium is phosphorylated and incorporated into DNA in MCF-7 breast cancer cells. We present a mechanistic analysis that defines purine nucleoside phosphorylase and ribonucleotide reductase as key enzymes in the salvage of 8-oxodG prior to its incorporation into both DNA and RNA. The data support that 8-oxodG in the nucleotide pool may substantially contribute to the formation of 8-oxoG in DNA. |
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General Papers
1:00 PM-4:45 PM, Wednesday, August 22, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |