The Control of Tumour Oxygenation in Mice: The Importance of Tumour Site

Abstract

Several bioreductive drugs have been shown to achieve impressive hypoxic/oxic toxicity ratios in vitro ^{1, 2}. Their impact when given alone as anti tumour agents in vivo has been much less impressive, as might be predicted for drugs whose effects are predominantly on the hypoxic cell fraction. It was recognised that some means of increasing the proportion of hypoxic cells in tumours would have to be used if a substantial cell kill was to be achieved. Published reports of this strategy have mainly focused on the modification of tumour blood flow as the means of increasing hypoxia. Several classes of compound are capable of reducing blood flow in rodent tumours^{3, 4}, but most studies involving the bioreductive cytotoxins have used either hydralazine or 5-HT^{5, 6, 7}. A major problem with this combination is that a collapse in blood flow prevents the access of further cytotoxin. Two other, distinctly different methods have been used to achieve an increased hypoxia in mouse tumours, neither of which prevents the access of the drug.