The aim of the study was to analyze whether therapeutic ROS induction may affect the stability of solid tumor tissue by promoting cell dissociation. In addition, a possible protective impact of a-tocopherol treatment was studied. DS-sarcomas of rats were treated with a combination of 44UC-hyperthermia, inspiratory hyperoxia and xanthine oxidase in order to induce oxidative stress. A second group of animals was pretreated with a- tocopherol. The expression of different adhesion molecules as well as the activity of matrix-degrading enzyme systems was measured. Expression of E-cadherin, the av-, b3-integrin and the avb3-integrin dimer was significantly reduced by ROS, an effect which was at least partially reversible by a-tocopherol pre- treatment. N-cadherin, a-catenin and the b5-integrin expression was not affected by ROS. MMP-2, MMP-9 and uPA activities were markedly reduced immediately after hyperthermia. Whereas 24 h later the effects on MMP-2 and -9 were no longer evident, for uPA the impact of oxidative stress became even more pronounced at this time. These results show that several processes responsible for the stability of tumor tissue are influenced by therapeutic ROS generation which may affect metastatic behavior. C.L., H.K.B., J.F.: Institute of Biological Chemistry, University of Hohenheim