REDUCING ACUTE AND CHRONIC HYPOXIA IN TUMORS BY COMBINING NICOTINAMIDE WITH CARBOGEN BREATHING

The ability of nicotinamide and carbogen breathing to improve the radi ation response of a C3H mammary carcinoma by reducing both acute and c hronic hypoxia was investigated. Using a tumour growth delay assay the response of 200 mm(3) foot tumours to local irradiation was found to be increased by either injecting nicotinamide (100-1000 mg/kg) 20 min prior to irradiation, or by allowing mice to breathe carbogen for 10 m in before and during the radiation treatment. The greatest radiosensit ization occurred when nicotinamide and carbogen were combined. With a histological fluorescent staining technique nicotinamide was shown to prevent transient stoppages in microregional blood flow, and also appe ared to improve tumour oxygenation as measured with an Eppendorf oxyge n electrode, both effects being consistent with its ability to decreas e perfusion limited acute hypoxia. Carbogen had no effect on vessel cl osure, but it significantly improved tumour oxygenation, which was ind icative of it reducing diffusion limited chronic hypoxia.