P 036 - Effect of urea in the reaction of nucleosides with hypobromous acid

Abstract

Hypobromous acid (HOBr) is generated by eosinophil peroxidase or myeloperoxidase using hydrogen peroxide, chloride, and bromide in the host defense system of humans, protecting against invading bacteria. Generally, HOBr can react with amines (R-NH2), resulting in bromamines (R-NHBr). Urea (CO(NH2)2) is a ubiquitous molecule with high concentrations (5 mM in plasma, 285 mM in urine) in humans. However, there is little information on the effect of urea in the reaction of HOBr. In the present study, we examined the reaction of nucleosides with HOBr in the absence and presence of urea using HPLC. Without urea, nucleosides immediately reacted with HOBr in the order of dG>dC>dT>dA. In the presence of 100 mM urea, the reaction was slow and carried out for several hours. 8-Br-dG, a reaction product from dG, increased by the addition of urea. Whereas, 100 mM lysine suppressed the reaction almost perfectly. The results suggest that urea reacts with HOBr resulting in urea bromamine, and which reacts with nucleosides slowly. Urea may have an importance for mutagenesis caused by the reaction of HOBr.