Increased cytotoxicity of low-dose, long-duration exposure to 5-fluorouracil of V-79 cells with hyperthermia.
We examined the cytotoxic effects of combined low dose and long exposure to 5-fluorouracil (5-FU) and hyperthermia on Chinese hamster V-79 cells with reference to timing and sequence of administration. The survival rate following hyperthermia at 42 degrees C for 2 h alone was 95.4%, and that after exposure to 1.0 micrograms/ml/5-FU alone for 48 hours, 94.2%. With respect to the combination of 5-FU and heat, the survival rate of cells exposed to hyperthermia at 42 degrees C for 2 h followed by 1.0 micrograms/ml 5-FU treatment for 48 h followed by hyperthermia led to a survival rate of 10%. Flow cytometric analysis of V-79 cells after exposure to 1.0 micrograms/ml 5-FU for 48 h revealed an accumulation of cells in the S-phase; the percentage of S-phase exponential growing cells was 65% and the plateau phase was 38%. The former were more sensitive to heat than the latter cells according to the MTT assay. V-79 cells pretreated with 5-FU were more sensitive to hyperthermia than were those not pretreated with 5-FU. Therefore, when 5-FU plus heat is to be used to treat a patient with a malignancy, the sequence of 5-FU followed by hyperthermia may be more effective than the reverse.
Kido
Y
Y
Department of Surgery II, Kyushu University, Fukuoka, Japan.
Kuwano
H
H
Maehara
Y
Y
Mori
M
M
Matsuoka
H
H
Sugimachi
K
K
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D006224:Cricetinae; D005434:Flow Cytometry; D005472:Fluorouracil / Q000008:administration & dosage / Q000633:toxicity*; D006979:Hyperthermia, Induced; D013696:Temperature; D013997:Time Factors
D005472:Fluorouracil