152785-98-3Relevant articles and documents
Peroxidase-catalyzed oxidative damage of DNA and 2′-deoxyguanosine by model compounds of lipid hydroperoxides: Involvement of peroxyl radicals
Adam, Waldemar,Kurz, Annemarie,Saha-Moeller, Chantu R.
, p. 1199 - 1207 (2000)
The peroxidase-catalyzed decomposition of 3-hydroperoxy-1-butene (1), 2,3-dimethyl-3-hydroperoxy-1-butene (2), tert-butyl hydroperoxide (3), ethyl oleate hydroperoxide 4, and linoleic acid hydroperoxide 5 was applied as a chemical model system to assess whether lipid hydroperoxides may cause DNA damage under peroxidase catalysis. For this purpose, the Coprinus peroxidase (CIP), horseradish peroxidase (HRP), and the physiologically important lactoperoxidase (LP) were tested. Indeed, hydroperoxides 1-5 induce strand breaks in pBR 322 DNA upon peroxidase catalysis. For the nucleoside dG, the enzymatic decomposition of hydroperoxides 1-4 led to significant amounts of 4,8-dihydro-4-hydroxy-8-oxo-2′deoxyguanosine (4-HO-8-oxo-dG) and guanidine-releasing products (GRP), whereas 7,8-dihydro-8-oxo-2′-deoxyguanosine (8-oxo-dG) was not obtained. In isolated calf thymus DNA, the efficient conversion of the guanine base (Gua) was observed. Peroxyl radicals, which are generated in situ from the hydroperoxides by one-electron oxidation with the peroxidases, are proposed as the active oxidants on the basis of the following experimental facts. (i) Radical scavengers strongly inhibit the guanine oxidation in dG and DNA and strand-break formation in the latter. (ii) EPR spectral studies with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap confirmed the formation of peroxyl radicals. (iii) The release of molecular oxygen was demonstrated, produced through the disproportionation of peroxyl radicals. The biological relevance of these findings should be seen in the potential role of the combined action of lipid hydroperoxides and peroxidases in damaging cellular DNA through peroxyl radicals.
Mechanistic and kinetic aspects of photosensitization in the presence of oxygen
Tanielian, Charles,Mechin, Robert,Seghrouchni, Rachid,Schweitzer, Claude
, p. 12 - 19 (2007/10/03)
Determining whether the first step of photooxygenation is Type I or Type II is a necessary prerequisite in order to establish the mechanism of photodynamic action. But this distinction is not sufficient, because other processes, both consecutive and competitive, commonly participate in the overall mechanism. Thus, in both Type I and Type II reactions, the initial products are often peroxides that can break down and induce free radical reactions. These aspects of photosensitization are discussed and illustrated by sensitizer/substrate systems involving (1) only radical reactions (decatungstate/alkane) and (2) reactions of singlet oxygen occurring in competitive and consecutive processes and possibly followed by radical reactions (methylene blue/2′-deoxyguanosine). Two other previously investigated systems involving, respectively, a Type II interaction followed by radical processes (methylene blue/alkene) and Type II reactions, some of which being competitive or consecutive (rose bengal/alkene), are briefly reconsidered.
Photochemistry and photobiology of furocoumarin hydroperoxides derived from imperatorin: Novel intercalating photo-fenton reagents for oxidative DNA modification by hydroxyl radicals
Adam, Waldemar,Berger, Maurice,Cadet, Jean,Dall'Acqua, Francesco,Epe, Bernd,Frank, Silvia,Ramaiah, Danaboyina,Raoul, Sebastian,Saha-Moeller, Chantu R.,Vedaldi, Daniela
, p. 768 - 778 (2007/10/03)
Photochemical and photobiological properties of the imperatorin-derived furocoumarin hydroperoxides 1a, 1a′, 2a and 2a′ have been investigated. Irradiation (350 nm) of the hydroperoxide 2a′ afforded the alcohol 2b (2%), a diastereomeric mixture of the hydroxy epoxide 2c (40%; diastereomeric ratio = 80:20) and the epoxide 2d (8%). The formation of these products was rationalized in terms of homolysis of the hydroperoxide bond initiated by intramolecular energy transfer from the photoexcited furocoumarin chromophore. The quantum yields for the photolytic decomposition of hydroperoxides were estimated to be in the range of 0.03-0.85 and decreased in the order 2a ? 2a′ ? 1a′ ≥ 1a. The involvement of hydroxyl radicals in these reactions was established by trapping experiments with benzene and spectroscopic evidence was obtained by EPR spin trapping with 5,5-dimethylpyrroline-N-oxide. Fluorescence titration, DNA melting and linear dichroism studies of furocoumarins indicated that these compounds undergo efficient complexation and also intercalation into the DNA. The binding parameters K (intrinsic binding constant) and 1/n (frequency of binding sites) of complexes between furocoumarin derivatives and DNA were determined to be in the range of 3900-23900 M-1 and 0.017-0.045. The photoreaction of 1a′ and 1b′ with 2′-deoxyguanosine (dGuo) afforded exclusively 7,8-dihydro-8-oxo-2′-deoxy-guanosine (8-oxodGuo), presumably through singlet oxygen, which was formed in a type II photooxidation process. In contrast, the hydroperoxide 2a oxidized dGuo to oxazolone as major and 8-oxodGuo as minor products through hydroxyl radicals, which were generated from 2a under photolytic conditions. Interestingly, the photoreactions of furocoumarins with salmon testes DNA showed that the highly reactive (φ = 0.85) hydroperoxide 2a is also most efficient in inducing the mutagenic DNA oxidation product 8-oxodGuo. Hence, the novel furocoumarin hydroperoxide 2a constitutes the first intercalating photo-Fenton reagent and serves as convenient hydroxyl radical source for genotoxicity studies.
