Thermoradiotherapy with hydralazine: The effect of preirradiation of the tumor bed on blood flow and growth delay of Ehrlich carcinoma

Ehrlich carcinoma transplanted into preirradiated calf muscle of mice was u sed as a model for tumor recurrence after unsuccessful radiotherapy. Due to the tumor bed effect (TBE), these grafts grew more slowly than control tum ors implanted in the unirradiated tissue. When these tumors achieved the sa me volume (0.3-0.4 cm(3)), in 10-11 days for tumors implanted in irradiated tissue and 7-8 days for control tumors, they were treated with radiation, the tumor blood how inhibitor hydralazine, and hyperthermia, alone or in di fferent combinations. In the case of the trimodality treatment, single irra diation of tumors at a dose of 12.5 Gy was followed 2.5-3 h later by admini stration of hydralazine (2.5 mg/kg) and local hyperthermia (water bath, 43 degrees C for 30 min). The growth delay induced in the different tumor type s by irradiation, hydralazine and hyperthermia, alone or in different combi nations, was related to the blood flow measured in the tumors by the Xe-133 clearance technique 24-48 h after treatment, It was shown that the reducti on of blood flow after treatment with hyperthermia or hydralazine was appro ximately equal in both types of tumors. However, the combined inhibiting ef fect of these agents differed in the tumors:: It was synergistic in control tumors and close to additive in tumors implanted in irradiated tissue. In terms of the specific tumor growth delay, the latter tumors were slightly m ore sensitive to hyperthermia, but were more resistant to radiation and the rmoradiotherapy compared to control tumors. Hydralazine potentiated the tum oricidal effects of heat alone and heat combined with radiation. The enhanc ement was more substantial in control tumors compared to tumors implanted i n irradiated tissue. A general correlation between the hydralazine-induced enhancement of the effects of heat on tumor blood how and growth delay was observed. In tumors implanted in irradiated tissue, the inhibition of perfu sion after treatment with hydralazine plus hyperthermia was smaller, and pr esumably a less marked treatment response to these agents (with or without radiation) was therefore achieved as a result in these tumors compared to t he control tumors. (C) 1999 bg Radiation Research Society.