Orcadian Gating of S Phase in Human Ovarian Cancer1

Cell proliferation in 30 patients with ovarian cancer was analyzed using flow cytometry to determine changes in the percentage of cells in S phase. By this measure, proliferation in tumor cells appears to follow a cyclical pattern of peaks and troughs that is out of phase with the Orcadian rhythm in proliferation of normal tissues. In round-the-clock monitoring of replication stages in tumor cells recovered from i.p. lavage fluid in postsurgery patients, peaks of tumor and nontumor cell DNA synthesis commonly occurred at different times of day. When patients were grouped so that only tumor cell proliferation was being measured, a highly significant 24-h rhythm nearly 12 h out of phase with nontumor cell proliferation was found. This peak in the percentage of S-phase cells occurs most commonly in midto late morning and appears to offer an opportunity for timing chemotherapy to coincide with high tumor cell vulnerability and low toxicity to normal tissue.