A formation mechanism for 8-hydroxy-2'-deoxyguanosine mediated by peroxidized 2'-deoxythymidine.
The oxidative formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in DNA is closely associated with the induction of degenerative diseases, including cancer. However, the oxidant species participating in the formation of 8-OHdG has yet to be fully clarified. On the basis that peroxyl radicals are a strong candidate for this species, we employed 2,2'-azobis(2-amidinopropane) (AAPH) as a peroxyl radical generator. Exposure of calf thymus DNA to AAPH formed 8-OHdG, but the exposure of 2'-deoxyguanosine (dG) alone did not. From the exposure of various combinations of nucleotides, 8-OHdG was formed only in the presence of dG and thymidine (dT). A mix of dG with an oxidation product of dT, 5-(hydroperoxymethyl)-2'-deoxyuridine, produced 8-OHdG, but the amount formed was small. In contrast, 8-OHdG was produced abundantly by the addition of dG to peroxidized dT with AAPH. Thus, the formation of 8-OHdG was mediated by the peroxidized dT. Instead of artificial AAPH, endogenous peroxyl radicals are known to be lipid peroxides, which are probably the oxidant species for 8-OHdG formation mediated by thymidine in vivo.
Goto
Miho
M
Laboratory of Food and Nutritional Chemistry, Graduate School of Science and Technology, Kobe University, Rokkodai, Nada-ku, Kobe 657-8501, Japan.
Ueda
Keisuke
K
Hashimoto
Takashi
T
Fujiwara
Shinji
S
Matsuyama
Kayo
K
Kometani
Takashi
T
Kanazawa
Kazuki
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000578:Amidines / Q000737:chemistry; D000818:Animals; D002417:Cattle; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D019281:Dimerization; D008928:Mitochondria / Q000378:metabolism; D008956:Models, Chemical; D016877:Oxidants / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010545:Peroxides; D013379:Substrate Specificity; D013936:Thymidine / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D000578:Amidines; D016877:Oxidants; D010545:Peroxides; C049375:perhydroxyl radical; C046728:2,2'-azobis(2-amidinopropane); D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen; D013936:Thymidine