Chemiexcited Neurotransmitters and Hormones Create DNA Photoproducts in the Dark.

In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide.

Cobalt-mediated oxidative DNA damage and its prevention by polyphenol antioxidants.

Although cobalt is a required nutrient, it is toxic due to its ability to generate reactive oxygen species (ROS) and damage DNA. ROS generation by Co often has been compared to that of Fe or Cu, disregarding the reduction potential differences among these metal ions. In plasmid DNA damage studies, a maximum of 15% DNA damage is observed with Co/HO treatment (up to 50 μM and 400 μM, respectively) significantly lower than the 90% damage observed for Fe/HO or Cu/HO treatment.

Triplet-Energy Quenching Functions of Antioxidant Molecules.

UV-like DNA damage is created in the dark by chemiexcitation, in which UV-activated enzymes generate reactive oxygen and nitrogen species that create a dioxetane on melanin. Thermal cleavage creates an electronically excited triplet-state carbonyl whose high energy transfers to DNA. Screening natural compounds for the ability to quench this energy identified polyenes, polyphenols, mycosporine-like amino acids, and related compounds better known as antioxidants.

Inactivating Gene Expression with Antisense Modified Oligonucleotides.

Modified nucleotides, including phosphoramidates and mesyl nucleotides, are very effective in inactivating gene expression in bacteria. is the target gene in several organisms, including . Antisense reactions with bacteria infecting citrus plants are promising but incomplete.

Polyphenol effects on CuO-nanoparticle-mediated DNA damage, reactive oxygen species generation, and fibroblast cell death.

The ability of ten polyphenolic antioxidants to prevent CuO nanoparticle (CuO) and HO-mediated DNA damage and cytotoxicity was investigated. Five of the polyphenols (MEPCA, PREGA, MEGA, ECG, and EGCG) prevent CuO/HO-mediated DNA damage (IC values of 7.5-800 μM), three have no effect (PCA, VA, and EC), and two (GA and EGC) result in increased DNA damage.

Reactive oxygen species generation by copper(II) oxide nanoparticles determined by DNA damage assays and EPR spectroscopy.

Copper(II) oxide nanoparticles (CuO) have many industrial applications, but are highly cytotoxic because they generate reactive oxygen species (ROS). It is unknown whether the damaging ROS are generated primarily from copper leached from the nanoparticles, or whether the nanoparticle surface plays a significant role. To address this question, we separated nanoparticles from the supernatant containing dissolved copper, and measured their ability to damage plasmid DNA with addition of hydrogen peroxide, ascorbate, or both.

Metal-mediated DNA damage and cell death: mechanisms, detection methods, and cellular consequences.

The redox activity of metal ions can lead to the formation of highly reactive species that damage DNA, producing different oxidation products and types of damage depending upon the redox potentials of the DNA bases, formation of intermediate adducts, and identity of the reactive species. Other factors are also important in determining the degree of metal-mediated DNA damage, such as localization and redox chemistry of the metal ions or complexes and lifetimes of the reactive oxygen species generated. This review examines the types of DNA damage mediated by first-row transition metals under oxidative stress conditions, with emphasis on work published in the past ten years.

Prevention of iron- and copper-mediated DNA damage by catecholamine and amino acid neurotransmitters, L-DOPA, and curcumin: metal binding as a general antioxidant mechanism.

Concentrations of labile iron and copper are elevated in patients with neurological disorders, causing interest in metal-neurotransmitter interactions. Catecholamine (dopamine, epinephrine, and norepinephrine) and amino acid (glycine, glutamate, and 4-aminobutyrate) neurotransmitters are antioxidants also known to bind metal ions. To investigate the role of metal binding as an antioxidant mechanism for these neurotransmitters, L-dihydroxyphenylalanine (L-DOPA), and curcumin, their abilities to prevent iron- and copper-mediated DNA damage were quantified, cyclic voltammetry was used to determine the relationship between their redox potentials and DNA damage prevention, and UV-vis studies were conducted to determine iron and copper binding as well as iron oxidation rates.