Becker T W, Krieger G, Witte I
Carl-von-Ossietzky Universität Oldenburg, Germany.
Free Radic Res. 1998 Jul;29(1):25-34. doi: 10.1080/10715769800300041.
The isomers n- and iso-butyraldehyde (BuA) in combination with Cu(II) induced single and double strand breaks in PM2 DNA, whereas the aldehydes, or Cu(II) alone had only negligible effect. The DNA damage was the 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. Characterization of DNA damage pointed to different ultimate DNA damaging species. While catalase and neocuproine inhibited strand break formation 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, sodium azide showed a high strand break inhibition in the n-BuA/Cu(II) reaction, but low inhibition in the iso-BuA/Cu(II) reaction. 2-Deoxyguanosine was hydroxylated in the 8-position by iso-BuA/Cu(II) but little reaction occurred with n-BuA/Cu(II). Chemiluminescence was detected during both BuA/Cu(II) reactions, whereby the intensity of the luminescence 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 proceeds via different pathways with different DNA damaging consequences. Whereas the oxidation of iso-BuA mainly results in damage by .OH-radicals, the oxidation of n-BuA may lead to a radical reaction chain whereby excited states are involved and the resulting DNA-damaging species are not .OH-radicals.
正丁醛和异丁醛（BuA）的异构体与铜（II）结合会导致PM2 DNA出现单链和双链断裂，而单独的醛类或铜（II）只有可忽略不计的影响。DNA损伤是醛类在形成铜（I）的过程中发生自由基氧化的结果。铜（I）的形成与分子氧无关。只有在分子氧存在的情况下才观察到广泛的DNA降解。对DNA损伤的表征表明存在不同的最终DNA损伤物种。虽然过氧化氢酶和新铜试剂在很大程度上抑制了异丁醛/铜（II）诱导的链断裂形成，但这些抑制剂在正丁醛/铜（II）反应中的效果较差。另一方面，叠氮化钠在正丁醛/铜（II）反应中表现出较高的链断裂抑制作用，但在异丁醛/铜（II）反应中的抑制作用较低。异丁醛/铜（II）使2-脱氧鸟苷在8位发生羟基化，但正丁醛/铜（II）与之反应很少。在两种丁醛/铜（II）反应过程中均检测到化学发光，其中正丁醛/铜（II）的发光信号强度比异丁醛/铜（II）高3.5倍。我们推测，铜（II）驱动的正丁醛和异丁醛氧化通过不同的途径进行，产生不同的DNA损伤后果。而异丁醛的氧化主要导致由·OH自由基造成的损伤，正丁醛的氧化可能导致自由基反应链，其中涉及激发态，并且产生的DNA损伤物种不是·OH自由基。
