nitroarginine and 2-thiomalic-acid

Reactive oxygen species have been shown to be involved in the mutagenicity, clastogenicity, and apoptosis of mammalian cells treated with arsenic or cadmium. As these endpoints require several hours of cellular processing, it is not clear that reactive oxygen species damage DNA directly or interfere with DNA replication and repair. Using single-cell alkaline electrophoresis, we have detected DNA strand breaks (DSBs) in bovine aortic endothelial cells by a 4-h treatment with sodium arsenite (As) and cadmium chloride (Cd) in sublethal concentrations. As-induced DSBs could be decreased by nitric oxide (NO) synthase inhibitors, superoxide scavengers, and peroxynitrite scavengers and could be increased by superoxide generators and NO generators. Treatment with As also increased nitrite production. These results suggest that As-increased NO may react with O2*- to produce peroxynitrite and cause DNA damage. The results showing that Cd increased cellular H2O2 levels and that Cd-induced DSBs could be modulated by various oxidant modulators suggest that Cd may induce DSBs via O2*-, H2O2, and *OH. Nevertheless, the DSBs in both As- and Cd-treated cells seem to come from the excision of oxidized bases such as formamidopyrimidine and 8-oxoguanine, as the Escherichia coli enzyme formamidopyrimidine-DNA glycosylase (Fpg) increased DSBs in cells treated with As, 3-morpholinosydnonimine (a peroxynitrite-generating agent), Cd, or H2O2.

Topics: Amitrole; Animals; Antioxidants; Aorta; Arsenites; Bacterial Proteins; Cadmium Chloride; Catalase; Cattle; Cells, Cultured; Chromans; Citrulline; Ditiocarb; DNA Damage; DNA-Formamidopyrimidine Glycosylase; Endothelium, Vascular; Enzyme Inhibitors; Escherichia coli Proteins; Free Radical Scavengers; Hydrogen Peroxide; Molsidomine; Mutagens; N-Glycosyl Hydrolases; Nitrates; Nitric Oxide; Nitric Oxide Donors; Nitric Oxide Synthase; Nitroarginine; Onium Compounds; Phenanthrolines; Reactive Oxygen Species; Sodium Compounds; Sodium Selenite; Superoxide Dismutase; Superoxides; Thiomalates; Thiourea; Uric Acid