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lüll Nitric oxide: perspectives and emerging studies of a well known cytotoxin Paradise WA; Vesper BJ; Goel A; Waltonen JD; Altman KW; Haines GK; Radosevich JAInt J Mol Sci 2010[Jul]; 11 (7): 2715-45The free radical nitric oxide (NO(*)) is known to play a dual role in human physiology and pathophysiology. At low levels, NO(*) can protect cells; however, at higher levels, NO(*) is a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NO(*) in cancer has to date been tissue-specific, we herein review underlying commonalities of NO(*) which may well exist among tumors arising from a variety of different sites. We also discuss the role of NO(*) in human physiology and pathophysiology, including the very important relationship between NO(*) and the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NO(*) in three main areas of epigenetics-DNA methylation, microRNAs, and histone modifications-is then discussed. Finally, we describe the recent development of a model cell line system in which human tumor cell lines were adapted to high NO(*) (HNO) levels. We anticipate that these HNO cell lines will serve as a useful tool in the ongoing efforts to better understand the role of NO(*) in cancer.|Animals[MESH]|Cytotoxins/metabolism/pharmacology[MESH]|Epigenesis, Genetic[MESH]|Glutathione S-Transferase pi/metabolism[MESH]|Humans[MESH]|Models, Biological[MESH]|Neoplasms/genetics/metabolism[MESH]|Nitric Oxide/*metabolism/pharmacology[MESH]|Reactive Nitrogen Species/metabolism[MESH] |