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The cytotoxicity of bleomycin in vitro has previously been shown to be enhanced by hyperthermia. This study demonstrates in vivo a synergistic interaction between local hyperthermia (43 degrees C, 45 min) and bleomycin (15 mg/kg) against implanted mammary tumors of C3H/He mice. Hyperthermia was given by water bath heating. When combined treatments of heat and bleomycin were administered within 30 min of each other, a synergistic effect was observed. In contrast, when the interval between heat and bleomycin injection was longer than 30 min, only an additive effect was obtained. Timing is therefore considered to be a critical factor for the optimal combination of hyperthermia and bleomycin.
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