Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis

Abstract

Superoxide radicals may induce genotoxic effects by indirect action mechanisms, implicating the formation of more long-lived, secondary clastogenic material called chromosome breakage factors or clastogenic factors (CF). CF are produced via the intermediacy of superoxide, and stimulate further superoxide production by competent cells. This results in a selfsustaining and longlasting process of clastogenesis, which may exceed the DNA repair system and ultimately lead to cancer. An increased cancer risk is indeed observed in conditions accompanied by CF formation. These include irradiated persons, asbestos workers, patients with chronic inflammatory diseases, HIV-infected persons, and the congenital breakage syndromes ataxia telangiectasia, Bloom's syndrome, and Fanconi's anemia. Because reactive oxygen species (ROS) are implicated in CF formation and CF action, antioxidants may be protective as anticlastogens and consequently as anticarcinogens. In persons at high risk because of their occupation, life style or place of residence, the presence of CF may represent an indication for chemoprevention of cancer by antioxidants. CF can be useful as biochemical markers and intermediate endpoints for the evaluation of promising drugs. They are therefore not only of interest as a mechanism by which ROS may exert genotoxic effects, but also have practical implications.