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.