8-Oxo-7,8-dihydro-2'-deoxyguanosine is not salvaged for DNA synthesis in human leukemic U937 cells.
8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG), the most common oxidatively modified nucleoside, is released from oxidized DNA and oxidized nucleotide pool. However, little information is available regarding the metabolic pathway of free 8-oxo-dG. In this study, we generated radiolabeled 8-oxo-dG to track its metabolic fate. We report that 8-oxo-dG is neither phosphorylated to 8-oxo-dGMP nor degraded to the free base, 8-oxo-7,8-dihydroguanine (8-oxo-Gua), indicating that 8-oxo-dG is not a substrate for nucleotide synthesis. This result was confirmed by the finding that no radioactivity was detected in the DNA of U937 cells after incubating the cells with radiolabeled 8-oxo-dG. These observations indicate that 8-oxo-dG produced by oxidative stress is not reutilized for DNA synthesis.
Seoul National University College of Medicine, Department of Pharmacology, South Korea.
Ja-Eun
JE
Kim
Myung-Hee
MH
Chung
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007938:Leukemia; D018384:Oxidative Stress / Q000502:physiology
D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA