RADIOSENSITIZATION BY CISPLATIN TREATMENT IN CISPLATIN-RESISTANT AND SENSITIVE HUMAN OVARIAN-CARCINOMA CELL-LINES

Abstract

The responses of cisplatin resistant (A2780(cp)) and cisplatin sensitive (A2780) ovarian carcinoma cell lines to radiation, cisplatin and cisplatin plus radiation have been studied. The cisplatin resistant cell line showed cross resistance to radiation. When cells were exposed to 2 mu g/ml of cisplatin treatment for one hour radiosensitization was achieved. The degree of radiosensitization was treatment sequence dependent. Irradiation followed by cisplatin treatment resulted in synergistic interaction with dose modifying factors (DMFs) as high as 1.5 in the resistant line and 1.1 in the sensitive line. The reverse sequence resulted in antagonistic interaction with DMFs of 0.8 to 0.9 at the 10% survival level. At lower survival levels the interaction remained antagonistic for the resistant cell line. Increasing the cisplatin concentration to 4 mu g/ml did not increase the degree of cisplatin radiosensitization. Simultaneous treatment of irradiation during the middle of a one or two hour cisplatin treatment did not increase the degree of radiosensitization. The cisplatin resistant cell line had a much greater cisplatin radiosensitization effect than the sensitive parental cell line with maximum DMFs for the resistant cell line ranging from 0.9-1.5 and for the sensitive cell line from 0.8-1.1. These results indicate that cisplatin may be an effective radiosensitizer especially in cisplatin resistant cell lines. This effect may be related to the inhibition of repair of radiation damage which may be elevated as a mechanism of resistance in the resistant cell line.