CHANGES IN TUMOR MORPHOLOGY WITH ALTERATIONS IN OXYGEN AVAILABILITY - FURTHER EVIDENCE FOR OXYGEN AS A LIMITING SUBSTRATE

The ability of cancer cells to survive at a distance from blood vessels should be dependent on the local supply of nutrients to each vessel. The corded growth of tumour cells around blood vessels within regions of necrosis in the RH carcinoma in the mouse allows the limit to which cells can be supported by individual vessels to be observed. The thickness of individual tumour cords was measured in conventionally stained tumour sections using a scanning technique to determine the distance between the blood vessel wall and the most distant viable cell adjacent to necrosis. Cord radius was found to vary with the oxygen supply conditions. Control animals had a mean radius of 105 +/- 2-mu-m while animals that had breathed 10% oxygen had significantly narrower cords (93 +/- 3-mu-m after 48 h) and animals breathing 100% oxygen had significantly wider cords (117 +/- 3-mu-m after 24 h). Mice made anaemic (mean htc. 28%) by phlebotomy and plasma transfusion had cord radii that were not significantly different from controls at any time up to 48 h. We conclude that this relatively slow growing mouse tumour is capable of rapid morphological adaptation (< 3 h) to changes in nutrient availability and that oxygen is probably the limiting substrate.