Chronic inflammation and reactive oxygen and nitrogen metabolism - Implications in DNA damage and mutagenesis

Abstract

It is well known that chronic inflammation of the digestive tract is associated with an increased risk of malignant transformation. Because phagocytic leukocytes and cytokine-activated parachymal cells produce large amounts of reactive metabolites of oxygen and nitrogen, there has been substantial interest in ascertaining whether these reactive intermediates may mediate mutagenesis and malignant transformation in vivo. However, very little information is available regarding the basic chemistry of how these oxygen and nitrogen-derived species may interact to yield potentially carcinogenic agents. This review will discuss our present understanding of the chemical and biochemical interactions between superoxide and nitric oxide and provide a model by which these reactive species may damage DNA and mediate mutagenesis.