Colcemid and the mitotic cycle.

The precise segregation of replicated chromosomes to daughter cells during mitosis depends on the formation of a bipolar spindle composed primarily of microtubules (MTs). Since MTs are highly dynamic structures whose spatial organization is critical for proper spindle function, physical and chemical agents that interfere with MT behavior invariably disrupt mitosis. Perhaps the most notable of these agents is colchicine, derived from plants of the genus Colchicum, which has long been known to be a potent inhibitor of cell division through its effects on spindle MT assembly (reviewed by Eigsti and Dustin, 1955; Dustin, 1978; Sluder, 1991). Over the years the action of colchicine, and the closely related but less-toxic compound demecolcine (Colcemid), has been mostly elucidated and other drugs (e.g. podophyllotoxin, steganacin, vinblastine, Nocodazole) have been discovered that interfere similarly with mitosis through their action on MTs (e.g. see Eigsti and Dustin, 1955; Deysson, 1968; Mareel and DeMets, 1984). The functional basis of how colchicine and Colcemid disrupt the spindle is now well understood (e.g. see Taylor, 1965; Wilson et al., 1976; Dustin, 1978; Mareel and DeMets, 1984). However, much of our knowledge of how mitosis proceeds in the presence of these drugs (C-mitosis; Levan, 1938) is based on cytological examinations of fixed cells conducted prior to 1955 (summarized by Eigsti and Dustin, 1955; Dustin, 1978). Although these pioneering studies provided fundamental data regarding the effects of colchicine/Colcemid on spindle formation in plants and animals, and established much of the terminology still used to characterize the process of C-mitosis, few addressed the ultimate fate of C-mitotics in animal tissues. Moreover, those that did failed to reach a consensus concerning the extent that colchicine/Colcemid permanently blocks cells in mitosis, or whether these drugs inhibit the disjunction (i.e. anaphasic separation) of replicated chromosomes. Both of these issues are germane to, and have been impacted by, recent and important findings on the control mechanisms by which the cell monitors progress through, and ultimately exits, mitosis (e.g. see Hartwell and Weinert, 1989; Murray and Kirschner, 1989). The aim of this commentary is to oultine the process of C-mitosis in plant and animal cells with an emphasis on new data that provide possible explanations for why various cell types behave differently during mitosis in the presence of drugs that disrupt MT function. Although our focus is on colchicine/Colcemid, many of the conclusions may be applicable to similar drugs that disrupt mitosis through their action on MTs.