Kinetics of cisplatin-induced apoptosis in murine mammary and ovarian adenocarcinomas.

There is mounting evidence to indicate that the mode of cell death known as apoptosis plays an important role in cancer therapy. Most supporting observations have come from experiments conducted in vitro, and it is important to extend such studies to in vivo systems. We have therefore evaluated the magnitude and kinetics of apoptosis induction in tumors from mice treated with cisplatin (CP). Two transplantable murine tumors were studied: a mammary adenocarcinoma, MCa-4, and an ovarian adenocarcinoma, OCa-1. Tumor-bearing mice were injected with various doses of CP, and specimens were obtained over several days. Apoptosis was scored by morphometric analysis of histological sections of the tumors using the features characteristic of cells undergoing this mode of cell death. The results showed a significant apoptotic response in both tumors within a few hours after injection of the drug. The kinetics were very broad, with apoptotic cells present over essentially the entire time course studied. Dose-response relationships for CP-induced apoptosis were compared to the tumor response measured in terms of tumor growth delay.