TIMING OF MAMMALIAN CELL CYCLE EVENTS

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The aim of this project is to reappraise the evidence for circadian cell kinetic changes in proliferation of human cancer cells in situ using modern methods, and to determine whether the proliferative activity of these tumor and nontumor cells changes in response to surgery or is perturbed by chemotherapy. Early attempts to make cell kinetic measurements in humans were limited by available methodology and, with few exceptions, ignored the circadian gating of cell proliferation. Tumor cells as well as normal tissues in patients with ovarian cancer show profound day to night variations in the percentage of cells in a phase that might be exploited for therapeutic benefit. Proliferation of tumor and nontumor diploid cells will be measured in patients with abdominal carcinomatosis prior to and following surgery and prior to and following chemotherapy using flow cytometry and fluorescence microscopy to measure DNA content, tumor specific antigen immunofluorescence, narrow angle and 90 degree scatter and BUdR immunofluorescence. Tumor cell proliferation maxima and kinetic indices will be compared with those taken from the bone marrow and the labeling and release of tumor cells from the solid tumor into the peritoneum will be measured.