2'-Deoxycytidine
glycols (5,6-dihydroxy-5, 6-dihydro-2'-deoxycytidine) are major products of the
hydroxyl radical-induced oxidation of 2'-deoxycytidine resulting from either a Fenton reaction or exposure to ionizing radiation. Because of their instability, however, the
glycols have not previously been characterized. Instead, the impetus has been placed on the primary decomposition products of 2'-deoxycytidine
glycols, which includes
5-hydroxy-2'-deoxycytidine,
5-hydroxy-2'-deoxyuridine, and 2'-deoxyuridine
glycols. Here, we have identified one of the four possible diastereomers of 2'-deoxycytidine
glycols by product analyses of decomposition products, (1)H NMR, and mass spectrometry. This glycol was observed to decompose with a half-life of 50 min at 37 degrees C in buffered neutral solutions and preferentially undergo
dehydration to
5-hydroxy-2'-deoxycytidine. The rate of decomposition was strongly dependent on pH (2-10) and the concentration of
phosphate ion (10-300 mM). Next, we report on the deamination of
cytosine glycols to
uracil glycols in oxidized
DNA using
acid hydrolysis and high performance liquid chromatography analysis with electrochemical detection to monitor
5-hydroxycytosine and
5-hydroxyuracil. The results showed that the lifetime of
cytosine glycols is greatly enhanced in
DNA (34-fold; half-life, 28 h), and that deamination accounts for at least one-third of the total decomposition. The relatively long lifetime of
cytosine glycols in
DNA suggests that this important class of
DNA oxidation products will be significantly involved in repair and mutagenesis processes.