DNA Damage by 3,6-Dihydropyrazine-2,5-Dipropanoic Acid, the Cyclic Dimerization Product of 5-Aminolevulinic Acid
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Priscila C. Teixeira
Abstract
5-Aminolevulinic acid (ALA) is a heme precursor that accumulates in lead poisoning and inborn porphyrias. It has been shown to produce reactive oxygen species upon metalcatalyzed aerobic oxidation and to cause oxidative damage to proteins, liposomes, DNA, and subcellular structures. Studies have also shown that ALA may condense to yield the cyclic product 3,6-dihydropyrazine 2,5-dipropanoic acid (DHPY). Here we propose that DHPY could be involved in DNA damage in the presence of high concentrations of ALA. Exposure of plasmid pUC19 DNA to low concentrations of DHPY (2 10 M) in the presence of 0.1 mM Cu[2+] ions causes DNA strand breaks, as demonstrated by agarose gel electrophoresis. It was also shown that in the presence of Cu[2+] ions DHPY is able to increase the oxidation of monomeric 2deoxyguanosine to form 8- oxo-7,8-dihydro-2deoxyguanosine as inferred from high performance liquid chromatography measurements using electrochemical detection. Addition of a metal chelator (bathocuproine, 0.5 mM), the DNA compacting polyamines spermidine (1 mM) and spermine (1 mM) or antioxidant enzymes such as superoxide dismutase (10 g/ml) and catalase (20 g/ml) protect the DNA against these damages. The data presented here are discussed with respect to the increased frequency of liver cancer in patients with acute intermittent porphyria.
Copyright © 2001 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Biological Activity of Mammalian Transcriptional Repressors
- Cloning and Characterisation of Chlorophyll Synthase from Avena sativa
- DNA Damage by 3,6-Dihydropyrazine-2,5-Dipropanoic Acid, the Cyclic Dimerization Product of 5-Aminolevulinic Acid
- Chicken Erythrocyte Pyrimidine 5-Nucleotidase: Purification and Characterization of the Subclass I Enzyme
- Coenzymes Q9 and Q10, Vitamin E and Peroxidation in Rat Synaptic and Non-Synaptic Occipital Cerebral Cortex Mitochondria during Ageing
- Membrane Activity of (Cys48Ser) Lung Surfactant Protein B Increases with Dimerisation
- Participation of Residue F552 in Domain III of the Protective Antigen in the Biological Activity of Anthrax Lethal Toxin
- Purification of Chrysancorin, a Novel Antifungal Protein with Mitogenic Activity from Garland Chrysanthemum Seeds
- Legumain Forms from Plants and Animals Differ in Their Specificity
- Assignment of the Complete Disulphide Bridge Pattern in the Human Recombinant Follitropin β -Chain
- The Small GTPase Ras Is Involved in Growth Factor-Regulated Expression of the α1 Integrin Subunit in PC12 Cells
- The Mouse Gap Junction Gene Connexin29 Is Highly Expressed in Sciatic Nerve and Regulated during Brain Development
- A Selenocysteine-Containing Peroxiredoxin from the Strictly Anaerobic Organism Eubacterium acidaminophilum
- Characterization of C-Terminally Truncated Human Tissue Inhibitor of Metalloproteinases-4 Expressed in Pichia pastoris
