Physiological Chemistry of Superoxide and Nitric Oxide Interactions

Abstract

Chronic inflammation of the colon and rectum is known to be associated with enhanced production of both nitric oxide (NO) and reactive oxygen species such as Superoxide (O2 -) and hydrogen peroxide (H2O2). Patients with long-standing ulcerative colitis are also known to be at increased risk of developing colorectal cancer. Although NO and reactive oxygen intermediates have been shown to modify DNA bases and to promote a wide array of mutagenic reactions, there is increasing evidence to suggest that the interaction between O2 - and NO may dictate the type of mutagenic reaction produced at sites where both free radicals are produced. In the absence of O2 -, NO derived nitrosating agents will N-nitrosate a variety of primary and secondary amines and promote the nitrosative deamination of DNA bases. Furthermore, these same NO-derived nitrosating agents will S-nitrosate certain thiol-requiring repair enzymes thereby inhibiting certain DNA repair proteins. As the flux of O2 - is increased, N- and S-nitrosation reactions are suppressed but oxidative chemistry is enhanced. Thus, depending upon the fluxes of each radical either nitrosation or oxidation chemistry may predominate. A fundamental understanding of the interaction between O2 - and NO may provide new insight in the mechanisms responsible for inflammation-induced DNA repair and damage.