Role of oxygen free radicals in cancer development

In aerobic life, oxidative stress arises from both endogenous and exogenous sources. Despite antioxidant defence mechanisms, cell damage from oxygen free radicals (OFR) is ubiquitous. OFR-related lesions that do not cause cell death can stimulate the development of cancer. This review discusses the effects of oxidative stress at the different stages of carcinogenesis. Mutagenesis through oxidative DNA damage is widely hypothesised to be a frequent event in the normal human cell. A large body of evidence suggests important roles of OFR in the expansion of tumour clones and the acquisition of malignant properties. In view of these facts, OFR may be considered as an important class of carcinogens. Therefore, the ineffectiveness of preventive antioxidant treatments, as documented in several recent clinical trials, is surprising. However, the difficulties of antioxidant intervention are explained by the complexity of both free radical chemistry and cancer development. Thus, reducing the avoidable endogenous and exogenous causes of oxidative stress is, for the present, the safest option. In the near future, new insights in the action of tumour suppressor genes and the DNA repair mechanisms may lead the way to additional tools against carcinogenesis from OFR.