Mechanism of Colchicine-Mitosis 397 



An over-all decrease in tumor respiration was one of the first bio- 

 chemical observations on colchicine. Its relation with the inhibition 

 of mitosis is not evident.^"' ^'"'' 



It has been demonstrated that a 1.2 X K* " '^^ soluiion of colchi- 

 cine inhibits dephosphorylation and the deamination of desoxyribonu- 

 clcotidev Desoxyribonuclease is also inhibited; however, the relation 

 of these facts to mitosis is by no means clear, and the concentrations 

 of colchicine are far greater than those effective in spindle poisoning.«o 

 In rats injected 0.2 mg. of the drug, a decrease of the alkaline phos- 

 j)hatase activity was recorded in liver tissue; there was no increased 

 disintegration of ribonucleic acid (RNA) .'^i The RNA content of 

 fibroblasts erowine ni vitro was decreased by colchicine.--^ Pyrophos- 

 phatase, an enzyme which was found in great quantities in a benzo- 

 pyrene-induced sarcoma in a rat, was inhibited after a colchicine in- 

 jection, though no action on the enzyme could be detected i)2 vitro. ^ 



Other work on changes in pinine metabolism, possibly linked 

 with the curative effect of colchicine in gout, demonstrates that, while 

 the nucleotidase of the intestine of calves was not affected, that of 

 human serum was inhibited. Xanthine-dehydrase was also inhibited 

 in guinea pigs, but the concentrations of colchicine (50 per cent and 

 more) A\ere far larger than those effective both in spindle poisoning 

 aiul in therapeutics.''^ 



Inhibition of dehydrogenase acti\ity by colchicine and sodium 

 cacodylate. another spindle poison, was reported in 1938,''^ but no 

 further data on this subject have been published since. A strong de- 

 crease of liver dioxvi^henylalanine-decarboxylase in rats, and of the 

 pressor amines of the adrenals,^' may be related to the general toxicity 

 reactions of the alkaloid (Chapter 7) . In vitro studies of rat liver 

 slices demonstrated an inhibition of creatine synthesis, and blocking 

 of the formation of p-aminohippuric acid from p-aminobenzoic acid. 

 The methylation of nicotinamide was also inhibited. There appeared 

 to be a relation between amount of drug and degree of inhibition. 

 The formation of creatine from guanidoacetic acid and L-methionine 

 was inhibited by 65 per cent by a lO'^M solution of colchicine.^-^ 



In plant material, enzymatic reactions, /// vitro, of malt diastase 

 were accelerated by the addition of colchicine; however, the rates of 

 conversion of sucrose by invertase were not influenced. ""^ In the ger- 

 minating grains of Triticinn acstivinn L., the acti\ity of amylase was 

 increased by 10" Af colchicine. No significant changes of photosyn- 

 thesis ha\e been detected. *- 



Some further results will be considered in the paragraphs on the 

 action of meso-'mo'^hoX (17.5-2) and adenosinetriphosphoric acid 

 (17.5-4) . It is evident at this point that no significant relation be- 

 tween enz\nie inactixation and spindle poisoning has been detected. 



