Contribution of transient blood flow to tumour hypoxia in mice

Tumours grown in mice typically exhibit regions of hypoxia believed to result from two different processes: chronic oxygen deprivation due to consumption/diffusion limitations, and periodic deprivation resulting from transient reductions in tumour blood flow. The relative contribution of each is, however, not generally known. We have addressed this issue in transplanted SCCVII squamous cell carcinomas in C3H mice, using a quantitative extension of the fluorescence 'mismatch' technique coupled with cell sorting from irradiated tumours. At least half of the vessels in these tumours exhibit transient perfusion changes. Additionally, a majority of the 15-20% of cells that are sufficiently hypoxic to be resistant to radiation in the SCCVII tumours appear to result from cyclic, not continuous (diffusion-limited) hypoxia. Since different strategies may be necessary to counteract cyclic hypoxia in tumours, the possibility of transient blood flow changes should not be ignored when planning cancer therapy for humans.