Free radicals in tumor promotion

The induction of cancer by chemicals proceeds through a series of stages as a normal cell transforms into a malignant neoplasm. Free radicals, particularly those derived from molecular oxygen, may participate throughout these transitions. In this article the evidence for the involvement of free radicals in some of the later events associated with carcinogenesis, namely, tumor promotion, are reviewed. Tumor promoters elicit the production of radicals by direct chemical generation and through the indirect activation of cellular metabolic sources. Both pathways may lead to the formation of a cellular prooxidant state. Studies with free radical scavengers demonstrate inhibition of biochemical and biological sequelae of tumor promoter exposure. Potential biological targets of radical attack include nucleic acids, proteins, and lipids and the possible role of radical-mediated modification of these biomolecules in tumor promotion is discussed.