INVOLVEMENT OF OXYGEN-FREE RADICALS IN ISCHEMIA-REPERFUSION INJURY TOMURINE TUMORS - ROLE OF NITRIC-OXIDE

Ischaemia-reperfusion (I/R) injury is a model system of oxidative stre ss and a potential anti-cancer therapy. Tumour cytotoxicity follows ox ygen radical damage to the vasculature which is modulated by tumour pr oduction of the vasoactive agent, nitric oxide (NO.). In vivo hydroxyl ation of salicylate, to 2,3- and 2,5-dihydroxybenzoate (DHBs), was use d to measure the generation of hydroxyl radicals (OH.) following tempo rary vascular occlusion in two murine tumours (with widely differing c apacity to produce NO.) and normal skin. Significantly greater OH. gen eration followed I/R of murine adenocarcinoma CaNT tumours (low NO. pr oduction) compared to round cell sarcoma SaS tumours (high NO. product ion) and normal skin. These data suggest that tumour production of NO. confers resistance to I/R injury, in part by reducing production of o xygen radicals and oxidative stress to the vasculature. Inhibition of NO synthase (NOS), during vascular reperfusion, significantly increase d OH. generation in both tumour types, but not skin. This increase in cytotoxicity suggests. oxidative injury may be attenuation by tumour p roduction of NO.. Hydroxyl radical generation following I/R injury cor related with vascular damage and response of tumours in vivo, but not skin, which indicates a potential therapeutic benefit from this approa ch.