Enhanced radiation killing by 5-fluorouracil of biliary tract cancer cell lines.
Despite the frequent clinical use of 5-fluorouracil (5-FU) in combination with radiotherapy for patients with biliary tract cancers, data remain scarce concerning specifically the influence of 5-FU on the sensitivity of these cancer cells to radiation. The present study was carried out to evaluate the effects of concomitant treatment with 5-FU on radiation-induced cell killing in two established human biliary tract cancer cell lines (Mz-ChA-2 and SK-ChA-1 cells). These lines were chosen as we have previously shown that SK-ChA-1 cells are significantly more resistant to both radiation and 5-FU than Mz-ChA-2 cells. Clonogenic survival was employed as the end-point for cell killing. Administration of 5-FU at LD50 doses to each cell line significantly enhanced radiation-induced cell killing. The enhancement ratio (ER) was obtained by dividing the radiation dose required to decrease the cell survival fraction to 37% (D0) by the dose to decrease cell survival to the same level when the cells were also treated with 5-FU. The ER in each of the cell lines was greater when they were incubated with 5-FU after radiation rather than prior to radiation. Longer exposure times with 5-FU resulted in enhanced radiation killing. The ER was significantly higher in the radioresistant cell line than in the radiosensitive line. These findings suggest that therapy with radiation and 5-FU may be of value as components of multidisciplinary treatment for biliary tract cancer. Protracted low dose exposure to 5-FU may prove to be most efficacious in enhancing the effects of radiation therapy.
Moon
Y
Y
Department of Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115, USA.
Todoroki
T
T
Ohno
T
T
Fukao
K
K
Little
J B
JB
D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D007928:Lethal Dose 50; D011829:Radiation Dosage; D011836:Radiation Tolerance; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000528:radiation effects
D005472:Fluorouracil