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

The responses of cisplatin resistant (A2780(cp)) and cisplatin sensiti ve (A2780) ovarian carcinoma cell lines to radiation, cisplatin and ci splatin 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 depe ndent. Irradiation followed by cisplatin treatment resulted in synergi stic 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 1 0% survival level. At lower survival levels the interaction remained a ntagonistic for the resistant cell line. Increasing the cisplatin conc entration to 4 mu g/ml did not increase the degree of cisplatin radios ensitization. Simultaneous treatment of irradiation during the middle of a one or two hour cisplatin treatment did not increase the degree o f radiosensitization. The cisplatin resistant cell line had a much gre ater cisplatin radiosensitization effect than the sensitive parental c ell 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 indi cate that cisplatin may be an effective radiosensitizer especially in cisplatin resistant cell lines. This effect may be related to the inhi bition of repair of radiation damage which may be elevated as a mechan ism of resistance in the resistant cell line.