Radical Damage in Nonrespiratory Organ Systems

Cellular Oj concentrations in the human body are precisely regulated to maintain adequate substrate for oxidative phosphorylation and other essential metabolic reactions while minimising the production of reactive oxygen species capable of damaging cellular DNA, lipids, and proteins. 

Increased oxidant formation is a significant contribution to disease and often an indispensable requirement, but not just an epiphenomenon. In carcinogenesis, chemoprevention of exocyclic DNA adducts by antioxidants was demonstrated by Nair et al. (1996). Primary prevention of cancer is not only to avoid hazardous exposures but also involves the intake of protective agents and modulation of the host s defence mechanisms before the onset of malignancy. 

Adaptive systems allowing to survive to moderate or even severe hypoxia involve an increase in the expression of genes coding for proteins responsible for anaerobic production of adenosine triphosphate, namely aldolase A (EC 4.1.2.13), enolase-a (EC 4.2.1.11), lactate dehydrogenase (EC 1.1.1.27), pyruvate kinase (EC 2.7.1.40), and glucose transporter-1 (Semenza et al. 1996). 

Several transcription factors have been reported to be involved in the response to hypoxic stress (for review see Minet et al. 2001). 

In cultured proximal tubular LLC-PKi cells, S-nitrosoglutathione induced HIE-la acounulation and concomitant DNA binding (Sandau et al. 

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Chapter 15 Radical Damage in Nonrespiratory Organ Systems... 

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