Effect of carnosine homocarnosine and anserine on hydroxylation of the guanine moiety in 2'-deoxyguanosine, DNA and nucleohistone with hydrogen peroxide in the presence of nickel(II).

Abstract

The oxidation of 2'-deoxyguanosine (dG) to 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in free dG and the dG residues of DNA and nucleohistone with H2O2 in the presence of Ni(II) and histidyl oligopeptides, carnosine, homocarnosine and anserine was studied at physiological pH. The oxidation of free dG with H2O2 was enhanced by the oligopeptides, but not by Ni(II) alone. Much greater enhancement was produced by equimolar mixtures of Ni(II) with any of the oligopeptides or with L-histidine. In contrast, the oxidation of dG residues in DNA and nucleohistone with H2O2 was not affected by the oligopeptides, but was enhanced by Ni(II). The latter enhancement remained practically unchanged when Ni(II) was accompanied by equimolar amounts of homocarnosine or anserine, whereas carnosine tended to attenuate that enhancement. The extent of formation of 8-OH-dG in free dG depended on time and concentration of H2O2 and was highest at pH 7.4. An electron spin resonance study of the reaction mixture containing H2O2, Ni(II), carnosine, homocarnosine and/or anserine provided evidence for the generation of .OH radical in the reaction media. Although it has previously been concluded that carnosine, anserine and homocarnosine might serve as anti-oxidants, the present study does not support that conclusion and shows that these compounds may even act as pro-oxidants, especially when they are complexed with Ni(II). The results suggest that carnosine, homocarnosine and anserine, by enhancing oxidation of the free dG pool, may potentiate the carcinogenic effects of Ni(II) since the resulting 8-OH-dG can be misincorporated into DNA and thus produce a mutagenic lesion.