Hyperthermia potentiates the cytotoxic activity of 1-hexylcarbamoyl-5-fluorouracil in sarcoma-180 cells and human malignant tumor cells.
The sunergic effects on sarcoma-180 (S-180) cells and on human malignant tumor cells between 1-hexylcarbamoyl-5-fluorouracil (HCFU), a lipophilic masked compound of 5-fluorouracil (5-FU), and hyperthermia were investigated. After the S-180 cells had been exposed to 77 microM of the drug for 3 days, with or without heat (43 degrees C) treatment for 2 hr, the succinate dehydrogenase (SD) activity was assayed to determine cell viability. The SD activity of S-180 cells treated with HCFU combined with heat decreased to about 7.8% of findings in the control cells. When the S-180 cells were implanted in a pad of the left posterior inferior foot of a mouse, the size of the tumor markedly decreased in case of exposure to HCFU and heat, compared with findings in other groups. Body weight of the mice remained stable after these procedures. Decrease in the SD activity of 6 human gastric cancers and 7 colorectal cancers exposed to HCFU combined with heat was compared with findings in the other groups. The SD activity markedly decreased when the cells were exposed to HCFU combined with heat. These results suggest that HCFU plus hyperthermia treatment is effective in the host with a malignancy and that the toxicity is minimal.
Kusumoto
T
T
Cancer Center, Kyushu University Hospital, Fukuoka, Japan.
Maehara
Y
Y
Sakaguchi
Y
Y
Kohnoe
S
S
Sugimachi
K
K
D000818:Animals; D015179:Colorectal Neoplasms / Q000201:enzymology / Q000628:therapy*; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006979:Hyperthermia, Induced; D051379:Mice; D012510:Sarcoma 180 / Q000201:enzymology / Q000628:therapy*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000628:therapy*; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D013385:Succinate Dehydrogenase; C017367:carmofur; D005472:Fluorouracil