Chronic inflammation and oxidative stress in human carcinogenesis
Article first published online: 24 SEP 2007
Copyright © 2007 Wiley-Liss, Inc.
International Journal of Cancer
Volume 121, Issue 11, pages 2381–2386, 1 December 2007
How to Cite
Federico, A., Morgillo, F., Tuccillo, C., Ciardiello, F. and Loguercio, C. (2007), Chronic inflammation and oxidative stress in human carcinogenesis. Int. J. Cancer, 121: 2381–2386. doi: 10.1002/ijc.23192
- Issue published online: 25 SEP 2007
- Article first published online: 24 SEP 2007
- Manuscript Accepted: 5 SEP 2007
- Manuscript Received: 16 JUL 2007
- chronic inflammation;
- oxidative stress;
- nitrosative stress;
A wide array of chronic inflammatory conditions predispose susceptible cells to neoplastic transformation. In general, the longer the inflammation persists, the higher the risk of cancer. A mutated cell is a sine qua non for carcinogenesis. Inflammatory processes may induce DNA mutations in cells via oxidative/nitrosative stress. This condition occurs when the generation of free radicals and active intermediates in a system exceeds the system's ability to neutralize and eliminate them. Inflammatory cells and cancer cells themselves produce free radicals and soluble mediators such as metabolites of arachidonic acid, cytokines and chemokines, which act by further producing reactive species. These, in turn, strongly recruit inflammatory cells in a vicious circle. Reactive intermediates of oxygen and nitrogen may directly oxidize DNA, or may interfere with mechanisms of DNA repair. These reactive substances may also rapidly react with proteins, carbohydrates and lipids, and the derivative products may induce a high perturbation in the intracellular and intercellular homeostasis, until DNA mutation. The main substances that link inflammation to cancer via oxidative/nitrosative stress are prostaglandins and cytokines. The effectors are represented by an imbalance between pro-oxidant and antioxidant enzyme activities (lipoxygenase, cyclooxygenase and phospholipid hydroperoxide glutathione-peroxidase), hydroperoxides and lipoperoxides, aldehydes and peroxinitrite. This review focalizes some of these intricate events by discussing the relationships occurring among oxidative/nitrosative/metabolic stress, inflammation and cancer. © 2007 Wiley-Liss, Inc.