Oxidised guanidinohydantoin (Ghox) and spiroiminodihydantoin (Sp) are major products of iron- and copper-mediated 8-oxo-7,8-dihydroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine oxidation.
8-Oxo-7,8-dihydroguanine (8-oxoGua), an important biomarker of DNA damage in oxidatively generated stress, is highly reactive towards further oxidation. Much work has been carried out to investigate the oxidation products of 8-oxoGua by one-electron oxidants, singlet oxygen, and peroxynitrite. This report details for the first time, the iron- and copper-mediated Fenton oxidation of 8-oxoGua and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). Oxidised guanidinohydantoin (Gh(ox)) was detected as the major product of oxidation of 8-oxoGua with iron or copper and hydrogen peroxide, both at pH 7 and pH 11. Oxaluric acid was identified as a final product of 8-oxoGua oxidation. 8-oxodGuo was subjected to oxidation under the same conditions as 8-oxoGua. However, dGh(ox) was not generated. Instead, spiroiminodihydantoin (Sp) was detected as the major product for both iron and copper mediated oxidation at pH 7. It was proposed that the oxidation of 8-oxoGua was initiated by its one-electron oxidation by the metal species, which leads to the reactive intermediate 8-oxoGua (+), which readily undergoes further oxidation. The product of 8-oxoGua and 8-oxodGuo oxidation was determined by the 2'-deoxyribose moiety of the 8-oxodGuo, not whether copper or iron was the metal involved in the oxidation.
White
Blánaid
B
National Centre for Sensor Research (NCSR), School of Chemical Sciences, Dublin City University, Dublin 9, Ireland.
Tarun
Maricar C
MC
Gathergood
Nicholas
N
Rusling
James F
JF
Smyth
Malcolm R
MR
D003300:Copper / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006151:Guanosine / Q000031:analogs & derivatives* / Q000737:chemistry; D006827:Hydantoins / Q000737:chemistry*; D008958:Models, Molecular; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000737:chemistry*
D006146:Guanidines; D006827:Hydantoins; D013141:Spiro Compounds; C467338:guanidinohydantoin; C408822:spiroiminodihydantoin; D006151:Guanosine; D006147:Guanine; D003300:Copper; D003849:Deoxyguanosine