Abstract: The 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.
Keywords: nitric oxide; epigenetics; cytotoxicity; high NO adaptation; oncogenetic
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Paradise, W.A.; Vesper, B.J.; Goel, A.; Waltonen, J.D.; Altman, K.W.; Haines, G.K., III; Radosevich, J.A. Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin. Int. J. Mol. Sci. 2010, 11, 2715-2745.
Paradise WA, Vesper BJ, Goel A, Waltonen JD, Altman KW, Haines GK, III, Radosevich JA. Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin. International Journal of Molecular Sciences. 2010; 11(7):2715-2745.
Paradise, William A.; Vesper, Benjamin J.; Goel, Ajay; Waltonen, Joshua D.; Altman, Kenneth W.; Haines, G. Kenneth, III; Radosevich, James A. 2010. "Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin." Int. J. Mol. Sci. 11, no. 7: 2715-2745.