The effects of carbogen and nicotinamide on intravascular oxyhaemoglobin saturations in SCCVII and KHT murine tumours

Abstract

Considerable effort has been focused on devising methods for manipulating tumour oxygenation and thereby improving tumour radiosensitivity. The combination of nicotinamide and carbogen has been proposed to oxygenate both chronically and acutely hypoxic cells in tumours. However, results have varied markedly with both tumour model and measurement technique. The current objectives were (1) to determine whether changes in radiosensitivity following oxygen manipulation correlated with changes in tumour oxygenation and (2) to assess whether oxygenation was preferentially improved in specific tumour micro-regions. Using two murine tumour lines, the SCCVII carcinoma and the KHT sarcoma, tumour intravascular HbO2 saturations were measured cryospectrophotometrically following nicotinamide, carbogen or the combination. Generally, nicotinamide had minor effects on oxygenation, arguing against a substantial effect on acute hypoxia, while carbogen and the combination produced marked and equivalent improvements in oxygen availability. These results demonstrate that changes in tumour radiosensitivity may not agree with corresponding changes in oxygenation, even within a given tumour model, and that the efficacy of a given manipulative agent may vary substantially with tumour line. One possible explanation for these findings is that different subpopulations of clonogenic vs non-clonogenic cells may be oxygenated by alternative treatments.