Increased tumor tissue pressure in association with the growth of rat tumors.

In order to elucidate further the mechanisms of central necrosis formation and drug delivery into tumor tissue, the interstitial fluid pressure in the normal subcutis and in rat ascites hepatoma AH109A and AH272 tumors was measured by means of a modified diffusion chamber technique. Using our apparatus for determining tissue pressures, we can obtain an exact zero reference-point and thus analyze daily changes in tumor interstitial fluid pressure. Tumor interstitial fluid pressure was found to be always positive and significantly higher than that in the normal subcutis, which was negative (P less than 0.001). The pressure increased with tumor growth. Highly significant correlations between the tumor size and the tumor interstitial fluid pressure were observed in both AH109A (r = 0.87; P less than 0.001) and AH272 (r = 0.86; P less than 0.001). The rate of increase in this pressure differed between AH109A and AH272 (P less than 0.001). It is concluded that the elevated interstitial fluid pressure in tumors could induce central necrosis and attenuate drug delivery to tumor tissue.