Free-Radical Processes in Multistage Carcinogenesis

Abstract

Rodent and human cells in culture, transformed in vitro by radiation or chemicals into malignant cells, afford us the opportunity to probe into early and late events in the neoplastic process at a cellular and molecular level. Transformation can be regarded as an abnormal expression of cellular genes. The initiating agents disrupt the integrity of the genetic apparatus altering DNA in ways that result in the activation of cellular transforming genes (oncogenes) during some stage of the neoplastic process. Events associated with initiation and promotion may overlap to some degree, but in order for them to occur, cellular permissive conditions prevail. Permissive and potentiating factors include free radicals, and thyroid hormone, and inadequate antioxidants. Protective factors which suppress the carcinogenic process include enzymatic and dietary antioxidants. These are constitutive under normal circumstances and can be induced under conditions of oxidative stress produced by a wide range of carcinogens.