The results obtained by us (1948a) with maleic acid as an inhibitor of mitosis have been developed in an attempt to prepare other mitotic inhibitors related to maleic acid; in particular we have investigated the antimitotic activity of substances in which the maleic acid residue is part of an aliphatic ring. The imides of maleic acid (I) and of citraconic acid (II), N-ethylmaleimide (III), -and in addition succinimide (IV) were chosen for this purpose.

No abstract

NATURE1009 was obtained by centrifuging and redissolved in isotonic saline at an alkaline pH. Paper electrophoresis of this solution yielded spots with mobilities equal to those of human globulins, but no spots with the mobility of albumin. Paper electrophoresis of the supernatant of tho original precipitate resulted in a single spot which migrated with human albumin at pH 8•6 and pH 7•4.Selective precipitation has been of limited value as a preparative tool because of possible alterations of the proteins, both those precipitated and those remaining in solution. However, our rc'3ults indicate that little, if any, alterations occur when ATP is used as the precipitating agent. This may have some limited application in the separation of proteins. Furthermore, it is felt that this reaction may have a bearing on the transport and storage of high-energy phosphate compounds.

The study of mitotic inhibition in experiments to be endowed with antimitotic properties, and dealing with toxicological and pharmacological conversely some mitotic poisons should be able to problems has been used by Dustin (1934) (1945, 1946) and later Huber (1947) taneously trapping the ribonucleate complex by with the eggs of Tubifex; Ltischer investigated the formation of an insoluble stilbamidine-ribonuregeneration in Xenopus larvae under the influence cleate. Nucleoproteins, therefore, can be inactiof colchicine. Barber and Callan (1943) studied vated by low concentrations of stilbamidine. Lettre the effect of cold and colchicine in mitoses of the and his collaborators (1946) found that substances newt.of the type R-Hg-X, where R is an alkyl or an From the beginning it was clear that the study aryl residue, X an inorganic or organic anion or of mitotic inhibitors may well pave the way for a phenol, are mitotic poisons. They explain the a chemotherapeutic approach to the cancer prob-antimitotic activity of these compounds by pointlems (Dustin, 1939). The great variety of anti-ing out that nucleic acids and nucleoproteins are mitotic substances and the lack of any chemical 'able to combine by salt or complex formation with connexion between many of them seemed to be the organometallic compounds to give insoluble a serious obstacle. Furthermore nearly all the products. The similarity in the mechanism by potent antimitotics are poisonous to normal cells which stilbamidine and the organometallic comat concentrations at which they exert antimitotic pounds disclose their antimitotic properties is action on tumour cells, in this way restricting the easily seen. They belong to the same physiological use of antimitotics to external application on sur-group of antimitotics, although they are chemically face tumours. Broderson (1943) has given evi-as dissimilar as possible. dence that it is possible by this method to control As mentioned above, the second great difficulty the growth of malignant tumours of the skin; he for the therapeutic utilization of antimitotics is the used colchicine, whose strong activity as a mitotic fact that the concentration at which they display inhibitor was well known. the antimitotic activity is nearly always within the Nevertheless these difficulties might be over-range of their toxicity for normal cells. Two ways come. Mitchell (1942)

(Mit'chell and Sin-lon-Reuss, 1947 ;Mitchell, 1948Mitchell, , 1949aMitchell, , 1949b 3,6, 12 and 24 hours after the 4th subeultivation, and then