Antioxidant-induced changes in oxidized DNA

Abstract

N-acetylcysteine (NAC), a strong antioxidant, has antigenotoxic and anticarcinogenic properties currently being investigated in clinical trials. NAC detoxifies free radicals (e.g., the hydroxyl radical, ⅐OH) that cause DNA changes implicated in disease (e.g., cancer). The ⅐OH reacts with purines to form mutagenic 8-hydroxypurine (8-OH) and putatively nonmutagenic formamidopyrimidine (Fapy) lesions. Fapy lesions inhibit DNA synthesis likely modulating the mutagenic potential of the 8-OH lesions, which would suggest that the ratio of these oxidized bases is biologically important. However, little is known about how NAC modifies oxidized DNA structure or how such modifications may affect cellular processes, such as replication and transcription. By using gas chromatography-mass spectrometry and Fourier transform-infrared spectroscopy, we found that dietary NAC (5% in the diet for 14 days) affected ⅐OH-induced structural changes in DNA of the hind leg of the BALB͞c mouse. For example, mutagenic 8-hydroxyguanine (8-OH-Gua) was reduced Ϸ50% (P ‫؍‬ 0.02) in mice fed NAC compared with controls. NAC reduced the log10 (8-OH-Gua͞FapyGua) ratio from 0.58 ؎ 0.15 to essentially zero, a virtually neutral redox status. DNA from control mice had a remarkably high variance compared with mice fed NAC. Moreover, the DNA from treated and control mice was distinct with respect to base structure and vertical base-stacking interactions. The findings showing that NAC lowered the concentration of 8-OH-Gua, the log ratio, and the variance (previously associated with neoplastic changes) suggest that NAC reduces the mutagenic potential of oxidized DNA. These benefits could be offset by the other structural changes found after NAC exposure, which may affect the fidelity of DNA synthesis.DNA damage ͉ free radicals ͉ N-acetylcysteine ͉ oxidation ͉ redox

Metabolic evidence for biogeographic isolation of the extremophilic bacterium Salinibacter ruber

“…Biogeography revealed after metabolomics R Rosselló-Mora et al present in Table 4 to provide a numerical perception of the group distance. The similarity within strains M8, M31, P13, P18 and IL3 (intensities for each m/z value) was evaluated first by using the Levene's test (Malins et al, 2002), which evaluates the differences (Pvalues) in the variances of each group of repetitions. Then, we used a one-way ANOVA, and a Tukey's test for repeated measures.…”

Quantitative measurement of hydroxyl radical induced DNA double‐strand breaks and the effect of N‐acetyl‐l‐cysteine

“…It has been proposed that the beneficial effect of NAC mainly comes from its capability of directly scavenging Å OH radicals as well as its function as a glutathione precursor [12][13][14][15][16][17]. However, there are still considerable controversies regarding the antioxidant efficacy of NAC.…”

DNA-damaging reagents induce apoptosis through reactive oxygen species-dependent Fas aggregation

“…We used three different free radicals scavengers to assess the role of ROS in cisplatin-induced apoptosis. C 60 (D3) is an effective scavenger of hydroxyl and superoxide radicals (Dugan et al, 1997;Hsu et al, 1998), MnTBAP is a superoxide dismutase mimic, and N-acetylcysteine (NAC) detoxifies free radicals to prevent DNA damage (Malins et al, 2002). C 60 (D3) effectively suppressed apoptosis induced by g-irradiation and cisplatin (Figure 7b).…”