|[Frontiers in Bioscience 2, d189-196, May 1, 1997]|
INTERACTIONS BETWEEN SUPEROXIDE AND NITRIC OXIDE: IMPLICATIONS IN DNA DAMAGE AND MUTAGENESIS|
David Jourd'heuil, David Kang and Matthew B. Grisham
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, LA 71130, USA
Received 4/3/97; Accepted 4/7/97; On-line 5/1/97
It is well known that chronic intestinal inflammation is associated with an increased risk of malignancy (1-3). This pathological condition might represent one prime example in which the chemistry we have described may play an important role. Indeed, the phagocytic leukocytes that accumulate within the chronically inflamed colon produce large amounts of O2- and NO which may mediate mutagenesis and possibly malignant transformation (1). Thus, the fundamental understanding of the interplay between O2- and NO may give us new insights into the chemical role that these two free radicals play during mutagenesis. In the absence of O2-, NO will N-nitrosate certain primary and secondary amines to yield potentially mutagenic nitrosamine intermediates (see Fig 5). In the presence of both NO and O2-, N-nitrosation chemistry may be suppressed but oxidation reactions may predominate.
Figure 5: Modulation of oxidative and nitrosative reactions by NO and O2-.