RADIOSENSITIVITY OF HUMAN BILIARY-TRACT CANCER CELL-LINES IN-VITRO

The prognosis of biliary tract cancer is still poor. Although a number of clinical studies have suggested a role for radiation therapy in ad vanced biliary tract cancer, its value remains controversial. Moreover , the intrinsic radiosensitivity of bile duct cancer cell lines has no t been described, and the molecular basis for the response of these tu mors to ionizing radiation is poorly understood. The present study was designed to examine the intrinsic radiation sensitivity of human bili ary tract cancer cells and its relationship to p53 status. Radiation r esponse expressed by the parameters n, D-0, D-10, alpha, beta, (D) ove r bar (mean inactivation dose), and SF, of seven cell lines derived fr om gallbladder and bile duct cancers was determined. The results sugge st that biliary tract cancer cell lines as a group are relatively radi oresistant. The mean X-ray survival parameters for these seven cancer cell lines were D-0=2.13+/-0.29 Gy, D-10=5.73+/-0.59 Gy, (D) over bar= 2.76+/-0.25 Gy, alpha=0.25+/-0.03, and SF2=0.54+/-0.05. One of the sev en lines was more radiosensitive than the others (D-0=0.77+/-0.02 Gy, D-10=2.95+/-0.06 Gy, (D) over bar=1.57 Gy, alpha=0.35, SF2=0.35+/-0.03 ). Five of six lines examined expressed mutant p53 including the radio sensitive line; one radioresistant line expressed wild-type p53. Thus, although loss of wild-type p53 expression occurred frequently in thes e biliary cancer cell lines, radiosensitivity did not correlate with p 53 status. In view of the intrinsic radioresistance of this type of tu mor cell coupled with the poor tolerance of surrounding normal tissues , maximal surgical debulking and intraoperative radiation therapy may contribute to increased local control over resection and/or convention al fractionated radiotherapy.