DIFFERENT DNA-DAMAGING SPECIES AS A RESULT OF OXIDATION OF N-BUTYRALDEHYDE AND ISO-BUTYRALDEHYDE BY CU(II)

The isomers n- and iso-butyraldehyde (BuA) in combination with Cu(II) induced single and double strand breaks in PM2 DNA, whereas the aldehy des, or Cu(II) alone had only negligible effect. The DNA damage was th e result of radical oxidations of the aldehydes under formation of Cu( I). Cu(I) formation was independent of molecular oxygen. Extensive DNA degradation was only observed in the presence of molecular oxygen. Ch aracterization of DNA damage pointed to different ultimate DNA damagin g species. While catalase and neocuproine inhibited strand break forma tion induced by iso-BuA/Cu(II) to a high degree, these inhibitors were less effective in the n-BuA/Cu(II) reaction. On the other hand, sodiu m azide showed a high strand break inhibition in the n-BuA/Cu(II) reac tion, but low inhibition in the iso-BuA/Cu(II) reaction. 2-Deoxyguanos ine was hydroxylated in the 8-position by iso-BuA/Cu(II) but little re action occurred with n-BuA/Cu(II). Chemiluminescence was detected duri ng both BuA/Cu(II) reactions, whereby the intensity of the luminescenc e signal was 3.5-fold higher for n-BuA/Cu(II) than for iso-BuA/Cu(II). We suppose that the copper(II)-driven oxidation of n- and iso-BuA pro ceeds via different pathways with different DNA damaging consequences. Whereas the oxidation of iso-BuA mainly results in damage by (OH)-O-. -radicals, the oxidation of n-BuA may lead to a radical reaction chain whereby excited states are involved and the resulting DNA-damaging sp ecies are not (OH)-O-.-radicals.