Effect of Tumor Hypoxia on Efficacy of Tirapazamine Combined with Fractionated Irradiation in Mouse Tumor

摘要

PURPOSE: Tumor hypoxia can be overcome with hypoxic cytotoxin. In mouse tumor, tirapazamine's efficacy of the potentiating radiation effect was tested by the tumor oxygenation status combined with hyperfactionated radiotherapy. MATERIALS AND METHODS: The control and hypoxic mouse tumors were established by inoculation of RIF-1 tumor cells into the normal or previously irradiated back and thigh of C3H mice. When the tumors reached a proper size, both the control and hypoxic tumors were given hyperfractionated treatments (8 fractions/4 days) with saline (0.02 ml/g), tirapazamin (0.08 mM/0.02 ml/kg), irradiation (2.5 Gy), irradiation combined with tirapazamine given 30 minutes prior to each irradiation. The response was evaluated by the growth delay assay by measuring tumor size from day 0 (12 hrs prior to the first fractionation) to the day when the volume had 4-fold increase or cross sectional area had 2-fold increase. RESULTS: Overall growth pattern showed that tirapazamine potentiated radiation effect in back and thigh tumors grew in the normal and preirradiated tumor bed. With growth delay assay using reference point of initial tumor volume or cross sectional area, tirapazamine potentiated radiation effect 1.9 times for the control and 2.4 times for the hypoxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. With reference of 4-fold increase of the initial volume or 2-fold increase of the cross sectional area, tirapazamine potentiated radiation effect 1.48 times for the control and 2.02 times for the hypxic tumors in back, and 1.85 times for the control and 1.6 times for the hypoxic tumors. CONCLUSION: Present result indicated that radiation response of hypoxic tumors was potentiated by tirapazamine in the back or thigh tumors grew in the control or preirradiated tumor bed, and potentiation of the hypoxic tumors was equal to or greater than that of the control tumors in the back or thigh.