Inflammation, carcinogenesis and cancer

To fulfill their role in host-defense, granulocytes secrete chemically reac tive oxidants, radicals, and electrophilic mediators. While this is an effe ctive way to eradicate pathogenic microbes or parasites, it inevitably expo ses epithelium and connective tissue to certain endogenous genotoxic agents . In ordinary circumstances, cells have adequate mechanisms to reduce the g enotoxic burden imposed by these agents to a negligible level. However, inf lammation persisting for a decade eventually elevates the risk of cancer su fficiently that it is discernible in case control epidemiological studies. Advances in our understanding of tumor suppressors and inflammatory mediato rs offer an opportunity to assess the molecular and cellular models used to guide laboratory investigations of this phenomenon. Disappointing results from recent clinical trials with anti-oxidant interventions raise questions about the risks from specific endogenous agents such as hydrogen peroxide and oxy radicals. Simultaneously, the results from the anti-oxidant trials draw attention to an alternate hypothesis, favoring epigenetic inactivation of key tumor suppressors, such as p53, and the consequent liability this p laces on genomic integrity. (C) 2001 Elsevier Science BN. All rights reserv ed.