KINETICS OF CISPLATIN-INDUCED APOPTOSIS IN MURINE MAMMARY AND OVARIANADENOCARCINOMAS

There is mounting evidence to indicate that the mode of cell death kno wn as apoptosis plays an important role in cancer therapy. Most suppor ting observations have come from experiments conducted in vitro, and i t is important to extend such studies to in vivo systems. We have ther efore evaluated the magnitude and kinetics of apoptosis induction in t umors from mice treated with cisplatin (CP). Two transplantable murine tumors were studied: a mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-I. Tumor-bearing mice were injected with various d oses of CP, and specimens were obtained over several days. Apoptosis w as scored by morphometric analysis of histological sections of the tum ors using the features characteristic of cells undergoing this mode of cell death. The results showed a significant apoptotic response in bo th tumors within a few hours after injection of the drug. The kinetics were very broad, with apoptotic cells present over essentially the en tire time course studied. Dose-response relationships for CP-induced a poptosis were compared to the tumor response measured in terms of tumo r growth delay. (C) 1995 Wiley-Liss, Inc.