Experimental study of thermochemotherapy. Mechanism of enhancement of cytotoxic effect of 1-hexylcarbamoy1-5-fluorouracil (HCFU) combined with hyperthermia.:Mechanism of enhancement of cytotoxic effect of 1-hexylcarbamoy 1-5-fluorouracil (HCFU) combined w

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Hydrolysis of 1-hexylcarbamoyl-5-fluorouracil (HCFU) to 5-fluorouracil (5-FU) is temperature dependent. We have previously reported the antitumor effects and cytotoxicity of HCFU combined with hyperthermia in vivo and in vitro. In vivo, we found that the highest 5-FU concentration in tumor tissue was produced by combined treatment with HCFU and hyperthermia. In this study, changes in membrane permeability to HCFU were studied at elevated temperature using Nakahara-Fukuoka sarcoma (NF-sarcoma) cells. There were significant increases in the rate of [14C] HCFU uptake at 42°C compared with control cells (37°C) treated for 30min. 1 hour and 1.5 hours, whereas the rate of [3H] 5 -FU uptake only increased slightly compared with control after heat treatment for various times. The efflux of [14C] HCFU and [3H] 5 -FU was unaffected by hyperthermia applied for various times. Therefore, the increased intracellular retention of HCFU that was caused by elevated temperature was attributed to an increase in influx. The magnitude of the increase in intracellular HCFU levels at elevated temperature was one factor involved in the great increase in cytotoxicity of HCFU.
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