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Effect of Dexamethasone on Vascular Function in RIF-1 Tumors¹

Department of Experimental Therapeutics, AMC Cancer Research Center, Lakewood, Colorado 80214

The present series of experiments was conducted to determine the effect of dexamethasone on vascular function and cell proliferation in s.c. RIF-1 tumors. ¹²⁵I-BSA, ⁵¹Cr-EDTA dilution techniques were used to evaluate dexamethasone induced changes in tumor plasma water, capillary permeability, and extracellular water volumes, while ⁵⁹Fe and ⁵¹Cr labeled erythrocyte techniques were used to assess changes in tumor exchangeable erythrocyte volumes. ⁸⁶RbCl distribution studies were also conducted to evaluate vascular perfusion in RIF-1 tumors after dexamethasone treatment. In this corticosteroid receptor containing tumor model, dexamethasone had profound effects on all of the measured parameters of vascular function. Reduced tumor cell proliferation after dexamethasone treatments was accompanied by reduced capillary permeability, reduced interstitial water volumes, increased plasma volumes, and reduced vascular perfusion. Serial studies after dexamethasone treatments indicated that increases in vascular perfusion preceded proliferative recovery. Intervals of maximal [³H]thymidine labeling after dexamethasone were characterized by transient increases in capillary permeability, interstitial water volumes, and tumor erythrocyte exchange with the general circulation. At intervals of maximal cell proliferation (36–48 h after dex) ³⁶RbCl distribution in tumors was about 3 times that seen in untreated controls. The results seem to indicate that, as in edematous normal tissues, dexamethasone can have profound effects on vascular function and water compartmentalization in RIF-1 tumors.

¹ This work was supported by a gift to the AMC Cancer Research Center from the Hill Foundation and by grant CA 34860 awarded by the Department of Health, Education, and Welfare.

Received 12/ 2/85. Revised 3/31/86. Accepted 4/ 3/86.

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