[In vivo cell cycle synchronization of the murine sarcoma 180 by continuous colcemid infusion (author's transl)].
In recent years, partial synchronization in vivo of normal tissues or solid tumors has been achieved by some investigators. A study of synchronization in vivo is valuable for not only analysis of the cell cycle kinetics, but also chemotherapy. Most of the chemotherapeutic agents and radiation show a specific reaction to a specific phase of cell cycle. This concept supports the value of chemotherapy using synchronization of tumor cells. In other words, the chemotherapeutic effect is enhanced by killing greater numbers of tumor cells which are gathered in a specific phase after synchronization. At the same time toxic effects are reduced by allowing normal tissue escaping from the effective phase. Colcemid is one of the most useful metaphase arrest agents. Colcemid blocks cells at metaphase by disrupting the mitotic spindle, and has been found to be less toxic than colchicine. Colcemid, when used in optimum dosage and duration of exposure, will accumulate tumor cells in metaphase with less toxic effects on normal tissues. Synchronization of the accumulated cells will be achieved after colcemid release. The purpose of this study is to examine the effects of colcemid on the cell cycle and to maximize synchrony after release of colcemid in sarcoma 180 tumor bearing mice. A mitotic linear accumulation was obtained by continuous colcemid infusion at 5.82 microgram/hr. Low dose colcemid infusion (0.582 and 1.455 microgram/hr) for 14 hours did not accumulated mitotic cells, but doses more than 5.82 microgram/hr of colcemid blocked it completely, accumulating 25.5% of cells after a 20 hours infusion. Therefore, mitotic accumulate by using colcemid is thought to be dose and time dependent within the limited range. However, the rates of mitotic accumulation were underestimated probably because of the increment of pyknoses and inhibition of DNA synthesis by high dose and long exposure of colcemid. A four hours colcemid infusion at 5.82 microgram/hr accumulated 11% of tumor cells without severe damage on cell cycle timing. The cells accumulated in mitotic phase recovered 3-4 hours after release of colcemid, and partial tumor synchronization was achieved in the following next one cycle. The rate of synchronization was thought to be about 30%, which was compatible with that of synchronization in vivo. Therefore, colcemid infusion at optimal dosage and duration of exposure can synchronize tumor cells reasonably. It is possible that therapeutic potential will be elevated if G1 or S phase specific drugs are used as killing agents after synchronization with colcemid. Moreover, higher synchrony will be obtained after several intermittent infusions of colcemid.
D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism; D003703:Demecolcine / Q000008:administration & dosage*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis / Q000187:drug effects*; D012510:Sarcoma 180 / Q000473:pathology*
D004273:DNA, Neoplasm; D003703:Demecolcine