title: Copper increases the damage to DNA and proteins caused by reactive oxygen species.
abstract: Copper [Cu(II)] is an ubiquitous transition and trace element in living organisms. It increases reactive oxygen species (ROS) and free-radical generation that might damage biomolecules like DNA, proteins, and lipids. Furthermore, ability of Cu(II) greatly increases in the presence of oxidants. ROS, like hydroxyl (.OH) and superoxide (.O(2)) radicals, alter both the structure of the DNA double helix and the nitrogen bases, resulting in mutations like the AT-->GC and GC-->AT transitions. Proteins, on the other hand, suffer irreversible oxidations and loss in their biological role. Thus, the aim of this investigation is to characterize, in vitro, the structural effects caused by ROS and Cu(II) on bacteriophage lambda DNA or proteins using either hydrogen peroxide (H(2)O(2)) or ascorbic acid with or without Cu(II). Exposure of DNA to ROS-generating mixtures results in electrophoretic (DNA breaks), spectrophotometric (band broadening, hypochromic, hyperchromic, and bathochromic effects), and calorimetric (denaturation temperature [T(d)], denaturation enthalpy [DeltaH], and heat capacity [C(p)] values) changes. As for proteins, ROS increased their thermal stability. However, the extent of the observed changes in DNA and proteins were distinct, depending on the efficiency of the systems assayed to generate ROS. The resulting effects were most evident when Cu(II) was present. In summary, these results show that the ROS, .O2 and .OH radicals, generated by the Cu(II) systems assayed deeply altered the chemical structure of both DNA and proteins. The physiological relevance of these structural effects should be further investigated.
authors.affiliation: Departamento de Bioquímica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico City, Mexico.
authors.forename: Martha Patricia
authors.initials: MP
authors.lastname: Cervantes-Cervantes
authors.forename: J Víctor
authors.initials: JV
authors.lastname: Calderón-Salinas
authors.forename: Arnulfo
authors.initials: A
authors.lastname: Albores
authors.forename: José Luis
authors.initials: JL
authors.lastname: Muñoz-Sánchez
mesh_terms: D010582:Bacteriophage lambda / Q000737:chemistry / Q000235:genetics; D002152:Calorimetry, Differential Scanning; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D004586:Electrophoresis; D005609:Free Radicals / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D011506:Proteins / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D005609:Free Radicals; D016877:Oxidants; D011506:Proteins; D017382:Reactive Oxygen Species; D003300:Copper; D004247:DNA