Cisplatin-induced enhancement of radioresponse in a murine mammary carcinoma:Test of a role for apoptosis

Programmed cell death or apoptosis has recently been recognized as an important mode of cell death in the response of tumor cells to cytotoxic treatments associated with chemotherapy or radiation therapy (RT). We previously showed that both cisplatin and radiation induced substantial apoptosis in the murine mammary tumor MCA-4 when administered as single agents in vivo. Moreover, the levels of apoptosis correlated with tumor response measured as tumor growth delay. In the current study a role for apoptosis in a combined treatment with cisplatin and radiation was evaluated. Mice bearing MCA-4 tumors were irradiated at different times following an injection with cisplatin, and tumor growth delay was assessed. Apoptosis was scored from histological sections of the tumors. The results showed that whereas the cisplatin sensitized the MCA-4 tumor to a subsequent irradiation in terms of the growth delay, the apoptotic index never rose above the maximum level characteristic of either agent when used singly. Thus, there was no indication that cisplatin sensitized the tumor cells to radiation-induced apoptosis. We conclude that apoptosis is not the only important mechanism for cell killing in tumors following cytotoxic treatment and that tumor response is a complex composite of many different factors. © 1995 Wiley-Liss, Inc.