Inflammation and oxidative stress in carcinogenesis.

Oxidants, which are generated by multiple pathways in mammalian organisms, may be natural carcinogens and contribute to several stages of malignant transformation. Active oxygen released by inflammatory phagocytes and more stable "clastogenic factors" can induce mutations and chromosomal aberrations in neighboring target cells. These oxidant-induced DNA sequence changes, though rare, may affect the activities of proto-oncogenes and suppressor genes. In addition, oxidants can promote cell growth. Like polypeptide growth factors they activate kinases. Because they break DNA, they also induce the poly ADP-ribosylation of chromosomal proteins. Both phosphorylation and poly ADP-ribosylation appear to participate in the transcriptional induction of the growth-related proto-oncogene c-fos. Growth stimulation by oxidants is modulated by the cellular antioxidant defenses. Maximal growth promotion is observed when cells are protected from excessive toxicity but still maintain a sufficient oxidant signal for the induction of growth-competence genes.