Oxidative stress and experimental carcinogenesis.

The focus of this review is to provide state-of-the-art knowledge on the involvement of oxygen free radicals (OFR) in carcinogenesis with a particular reference to skin model system as the process of cancer development is best understood in this organ. However, a brief description of the role of OFR in other organs is also provided. The term OFR refers to forms of oxygen exhibiting high reactivity and having at least one unpaired electron. The role of OFR in different stages of carcinogenesis such as initiation, promotion and progression is described. Out of many mechanisms described for the chemical initiation of tumorigenesis, a number of them may involve free radicals in the cascade of reactions. Evidences that support the involvement of free radicals in tumor promotion include (i) a number of free radical-generating compounds are found to be tumor promoters in various animal model systems, (ii) ROS generating systems can mimic the biochemical action of tumor promoters, (iii) some tumor promoters stimulate the production of ROS, (iv) tumor promoters modulate the cellular antioxidant defense systems, and (v) free radical scavengers, detoxifiers and antioxidants inhibit the process of tumor promotion. The role of ROS in the progression stage of carcinogenesis is evident from the fact that a number of different free radical generating compounds enhance the malignant conversion of benign papillomas into carcinoma and their effectiveness may be related to the type of radicals produced into the biological system.