Formation of 1,4-Dioxo-2-butene-Derived Adducts of 2'-Deoxyadenosine and 2'-Deoxycytidine in Oxidized DNA
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- 作者：Bingzi Chen ; Choua C. Vu ; Michael C. Byrns ; Peter C. Dedon ; Lisa A. Peterson
- 刊名：Chemical Research in Toxicology
- 出版年：2006
- 出版时间：August 2006
- 年：2006
- 卷：19
- 期：8
- 页码：982 - 985
- 全文大小：66K
- 年卷期：v.19,no.8(August 2006)
- ISSN：1520-5010
文摘
Oxidation of deoxyribose in DNA produces a variety of electrophilic residues that are capable of reactingwith nucleobases to form adducts such as M1dG, the pyrimidopurinone adduct of dG. We now reportthat deoxyribose oxidation in DNA leads to the formation of oxadiazabicyclo(3.3.0)octaimine adducts ofdC and dA. We previously demonstrated that these adducts arise in reactions of nucleosides and DNAwith trans-1,4-dioxo-2-butene, the 
-elimination product of the 2-phosphoryl-1,4-dioxobutane residuearising from 5'-oxidation of deoxyribose in DNA, and with cis-1,4-dioxo-2-butene, a metabolite of furan.Treatment of DNA with enediyne antibiotics capable of oxidizing the 5'-position of deoxyribose(calicheamicin and neocarzinostatin) led to a concentration-dependent formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA, while the antibiotic bleomycin, which is capable of performingonly 4-oxidation of deoxyribose, did not give rise to the adducts. The nonspecific DNA oxidant, 
-radiation,also produced the adducts that represented ~0.1% of the 2-phosphoryl-1,4-dioxobutane residues formedduring the irradiation. These results suggest that the oxadiazabicyclo(3.3.0)octaimine adducts of dC anddA could represent endogenous DNA lesions arising from oxidative stresses that also give rise to otherDNA adducts.
-elimination product of the 2-phosphoryl-1,4-dioxobutane residuearising from 5'-oxidation of deoxyribose in DNA, and with cis-1,4-dioxo-2-butene, a metabolite of furan.Treatment of DNA with enediyne antibiotics capable of oxidizing the 5'-position of deoxyribose(calicheamicin and neocarzinostatin) led to a concentration-dependent formation of oxadiazabicyclo(3.3.0)octaimine adducts of dC and dA, while the antibiotic bleomycin, which is capable of performingonly 4-oxidation of deoxyribose, did not give rise to the adducts. The nonspecific DNA oxidant, -radiation,also produced the adducts that represented ~0.1% of the 2-phosphoryl-1,4-dioxobutane residues formedduring the irradiation. These results suggest that the oxadiazabicyclo(3.3.0)octaimine adducts of dC anddA could represent endogenous DNA lesions arising from oxidative stresses that also give rise to otherDNA adducts.