Nitric oxide: perspectives and emerging studies of a well known cytotoxin.

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.