Abstract:
:Conversion of the 2'-deoxyguanosine (dG) residues in calf thymus DNA to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) was achieved at physiological pH by treating the DNA with hydrogen peroxide (H2O2) in the presence of nickel(II) chloride (NiCl2). The effectiveness of this reaction was enhanced by L-histidine (His) which forms the Ni(II)-His2 complex. Similar effects of NiCl2 and His were observed on hydroxylation of pure dG with H2O2. The rate of pure dG conversion to 8-OH-dG at 37 degrees C (100 mM phosphate buffer) depended on combination and concentration of the reagents and on pH. Following 24 h incubation at pH 7.4 of 0.75 mM dG with 30 mM H2O2 and 1 mM NiCl2, dG was converted into 8-OH-dG to the extent of 0.05% in the absence of His and 0.45% in the presence of 2 mM His. After 24 h incubation at pH 7.4 of 0.5 mg/ml DNA with 7.5 mM H2O2 and 0.1 mM NiCl2, 0.18% of the dG moiety was converted into 8-OH-dG in the absence of His and 0.42% in the presence of 0.2 mM His. Interestingly, a mixture of H2O2 with His was also capable of oxidizing dG to 8-OH-dG even in the absence of NiCl2, albeit less effectively than in the presence of NiCl2. This effect was not suppressed after treatment of dG, His and the buffer with Chelex to remove divalent metal contaminants, if any. The exact chemistry of the observed phenomena remains to be determined. Since the Ni(II)-His2 complex is the major low mol. wt nickel carrier in mammalian organisms, the observed redox properties of this complex, reported here for the first time, may be crucial for the toxicity and carcinogenicity of nickel.
journal_name
Carcinogenesisjournal_title
Carcinogenesisauthors
Dutta AK,Misra M,North SL,Kasprzak KSdoi
10.1093/carcin/13.2.283subject
Has Abstractpub_date
1992-02-01 00:00:00pages
283-7issue
2eissn
0143-3334issn
1460-2180journal_volume
13pub_type
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