Mr. Horsman et al., REDUCING ACUTE AND CHRONIC HYPOXIA IN TUMORS BY COMBINING NICOTINAMIDE WITH CARBOGEN BREATHING, Acta oncologica, 33(4), 1994, pp. 371-376
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.