Oxidative stress and inducible nitric oxide synthase induction in carcinogenesis

Chronic inflammation is linked to an increased risk of cancer. The molecular mechanisms underlying this correlation have been long investigated and it is well known that the inflammatory cells recruited in the inflamed tissues release chemical mediators, in particular reactive oxygen species (ROS). With respect to digestive systems, ROS have been implicated in a number of pathologies, including Helicobacter pylori-related gastritis, Barrett's esophagus, inflammatory disease of the lower gastrointestinal tract, alcoholic liver disease and several other types of toxic and virus-mediated liver injury. ROS levels within cells and tissues are controlled by numerous antioxidant defense mechanisms, but in inflammation, ROS overproduction exceeds defenses and damage intracellular macromolecules, including nucleic acids, with formation of potentially mutagenic and carcinogenic DNA adducts.

This paper summarizes our own experience investigating the link between inflammation, ROS production and oxidative DNA damage as well as the impact of the above events on cytokine and growth factor release, oncogene activation, telomere instability and microRNA in H. pylori-related gastritis, Barrett's esophagus and, in particular, hepatitis C virus-related liver disease. The paper also describes, at least in part, the complex scenario involving nitric oxide production and its impact in some gastrointestinal diseases, as well as a number of other molecular and biochemical changes related to ROS production and inflammation.

The paper falls obviously short of being an exhaustive summary of our understanding, but the data reported are intended as a stimulus to broaden the knowledge on the topic, also in view of the possible therapeutic implications of any advance obtained.