APOPTOSIS IN MURINE TUMORS TREATED WITH CHEMOTHERAPY AGENTS

There is increasing attention directed to the hypothesis that apoptosi s plays a role in the response to cancer treatment including chemother apy. However, the evidence to support this hypothesis has come almost entirely from experiments conducted in cultured cell systems. To exten d this hypothesis to the therapeutic setting it is necessary to addres s this critical question in tumors treated in vivo. We have therefore evaluated the extent of apoptosis induced in murine tumors treated in vivo with cancer chemotherapy agents. Seven different murine tumors, c omprising a mammary adenocarcinoma (MCa-4), an ovarian adenocarcinoma (OCa-1), a lymphoma (LY-TH), three sarcomas (FSA, NFSA and SA-NH) and a squamous cell carcinoma (SSC-7), were examined 8 and 24 h after trea tment with cisplatin or cyclophosphamide (CY). Apoptosis was scored by morphometric analysis of histological sections of the tumors. The res ults showed that MCa-4, OCa-1 and LY-TH had a significant apoptotic re sponse to both cisplatin and CY, and the other tumors had essentially no apoptotic response. In addition, two of these tumors, MCa-4 and OCa -1, underwent apoptosis in response to adriamycin, 5-fluorouracil, Ara -C, etoposide, camptothecin and fludarabine. These observations demons trate that apoptosis may be a feature of tumor response to chemotherap y in vivo, and illustrate the heterogeneity of apoptotic response amon gst different tumor types and to different cytotoxic agents.