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Int. J. Mol. Sci. 2010, 11(7), 2715-2745; doi:10.3390/ijms11072715
Review

Nitric Oxide: Perspectives and Emerging Studies of a Well Known Cytotoxin

1,2
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1,2
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3
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4
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5
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III 6
 and
1,2,*
1 Center for Molecular Biology of Oral Diseases, College of Dentistry, University of Illinois at Chicago, Chicago, IL 60612, USA 2 Department of Jesse Brown, Veterans Administration Medical Center, Chicago, IL 60612, USA 3 Division of Gastroenterology, Department of Internal Medicine, Charles A. Sammons Cancer Center and Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75246, USA 4 Department of Otolaryngology, Wake Forest University, Winston-Salem, NC 27157, USA 5 Mount Sinai School of Medicine, New York, NY 10029, USA 6 Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA
* Author to whom correspondence should be addressed.
Received: 26 May 2010 / Revised: 17 June 2010 / Accepted: 13 July 2010 / Published: 16 July 2010
(This article belongs to the Special Issue Advances in Molecular Toxicology)
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Abstract

The free radical nitric oxide (NO) is known to play a dual role in human physiology and pathophysiology. At low levels, NOcan protect cells; however, at higher levels, NOis a known cytotoxin, having been implicated in tumor angiogenesis and progression. While the majority of research devoted to understanding the role of NOin cancer has to date been tissue-specific, we herein review underlying commonalities of NOwhich may well exist among tumors arising from a variety of different sites. We also discuss the role of NOin human physiology and pathophysiology, including the very important relationship between NOand the glutathione-transferases, a class of protective enzymes involved in cellular protection. The emerging role of NOin 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 NOin cancer.
Keywords: nitric oxide; epigenetics; cytotoxicity; high NO adaptation; oncogenetic nitric oxide; epigenetics; cytotoxicity; high NO adaptation; oncogenetic
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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