Enhancement of cytotoxicity by hyperthermia after a long-term culture with 5-fluorouracil in transformed cells.
The cytotoxic effect of 5-FU (5-fluorouracil) was demonstrated to be enhanced by hyperthermia after treatment with 5-FU at even a comparatively low dose over fairly long periods. The cytotoxic effect of the combined treatment with 42 degrees C-hyperthermia and 1 microgram/ml 5-FU for 48 hrs, the cytotoxic effect of 42 degrees C-hyperthermia and 5 micrograms/ml 5-FU for 24 hrs, and the cytotoxic effect of 43 degrees C-hyperthermia and 1 and 5 micrograms/ml 5-FU for 8 hrs were studied. The maximally enhanced rate of 42 degrees C-hyperthermia after 5-FU treatment for 96 hrs was 48% after a 1 microgram/ml 5-FU treatment and 150% after 45 hrs with the 5 micrograms/ml 5-FU treatment. The maximally enhanced rate of 43 degrees C-hyperthermia after 5-FU treatment was 170% after 45 hrs with 1 microgram/ml 5-FU treatment and 180% after 24 hrs with 5 mg/ml 5-FU treatment. When V-79 cells were treated at the same temperature, the maximally enhanced rate with 1 microgram/ml 5-FU was almost equal to that of 5 micrograms/ml. Moreover, when each maximally enhanced rate was equalized, each concentration of FU (RNA)/RNA practically became equal, i.e., when the maximally enhanced rates were approximately 150 and 170-180%, FU (RNA)/RNA concentrations were about 40 and 15 ng/mg RNA, respectively. We thus concluded that FU (RNA)/RNA concentration might play an important role as an indicator of the effect of the combined treatment of 5-FU and hyperthermia.
D000818:Animals; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D006979:Hyperthermia, Induced; D007700:Kinetics; D012313:RNA / Q000096:biosynthesis; D013997:Time Factors
D012313:RNA; D005472:Fluorouracil