Nuclear Abnormalities Resulting from Inhibition of Mitosis by Colchicine and other Substances

Attention has been called, during the past few years, to the striking phenomenon of mitotic inhibition which occurs as a result of injecting certain substances into living animals and tissue cultures. The most striking effects of this sort occur, as originally described by Dustin (1), following treatment with sodium cacodylate and with the alkaloid colchicine. After the administration of these substances, large numbers of abnormal mitotic figures appear in all tissues, both normal and malignant, in which cell divisions normally occur in appreciable numbers. There is general agreement that these abnormal figures are characterized in all cases by the absence of the spindle, and Ludford (2) has attributed the suspension of division to the failure of that mechanism of which the spindle is the visible attribute. If we examine a slide of mouse sarcoma No. 180 from an animal which was injected with 0.025 mg. of colchicine ten hours previously, we see that about 12 per cent of the cells are in mitosis, in contrast to the normal figure of about 1 or 2 per cent (Fig. 1). When viewed superficially, many of these figures are not very different in appearance from normal figures, but upon careful observation it appears that there is no vestige of a spindle mechanism in the great majority of these cells, that the incidence of late stages (anaphases and telophases) is relatively much reduced, and that the chromosomes, although usually clumped together in a position suggestive of the normal early metaphase, are frequently somewhat scattered and clumped into many groups of different sizes. Detailed examination of this tumor shows certain note-worthy features. In the first place, the incidence of arrested mitotic figures is much higher around the periphery of the tumor than it is near the center, remote from the blood supply. A diagram of this tumor shows the percentage of dividing cells in nine selected areas, in each of which about 1000 cells were counted. The frequency is seen to be relatively low at the extreme periphery, where there are some normal cells mingled with sarcoma cells (Fig. 2). It reaches a maximum just below this point, and then shades off to figures in the center of the tumor which are not unlike those found in normal tissues. This may be due either to the fact that mitosis is less prevalent in the central portion of the tumor, normally, or that the drug fails to penetrate the entire 5 or 6 mm. of tissue; actually both factors are probably active.