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Publisher Summary This chapter discusses the DNA Damage and genotoxicity by nitric oxide (NO). The murine macrophages disclosed a novel enzymatic pathway that involved the oxidation of guanido nitrogen of L-arginine to nitric oxide. NO. undergoes subsequent oxidations and is excreted as urinary nitrate. The cell-signaling capability of NO. is related to its ability to diffuse from one cell to a neighboring cell. Although a variety of mechanisms may ultimately prove to be involved in nitric oxide-related damage to DNA, three types of reactions are focused: (1) indirect interactions with electrophiles arising from metabolism of endogenously formed N-nitrosamines, (2) direct nitrosation of primary amines on nucleic acid bases, and (3) attack by active species arising from reactions of NO with endogenous oxygen radicals. The chemistry of cellular damage by NO, although potentially complex to the overall mechanisms and the actual alterations of the nucleic acid, arise from two fundamental processes such as reaction with oxygen to form nitrosating species that may lead to deamination of DNA and the formation of N-nitroso compounds, and the reaction with superoxide to form peroxynitrite that may lead to oxidation of DNA. |
