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: cytotoxicity; epigenetics; high NO adaptation; nitric oxide; oncogenetic.