770 6. ARSENICALS 



evidence of growth stimulation was observed at any concentration, in 

 contrast to the reports occasionally made that arsenite accelerates mitosis 

 at very low levels. 



Mitotic inhibition may arise by different mechanisms and it is first nec- 

 essary to inquire whether the action of the arsenicals is primarily on the 

 cytoplasm or on the nucleus. Arsinites and arsonates potently interfere 

 with cell division in fibroblast cultures and the mitotic aberrations are of 

 two general types: (1) a colchicine-like effect on the spindle with metaphase 

 arrest, scattering of the chromosomes in the cytoplasm, and failure in equa- 

 torial constriction, and (2) an effect mainly on the chromosomes, manifested 

 by distortion and fusion, separation irregularities (bridges and stickiness), 

 and occasional fragmentation (King and Ludford, 1950). The dialkyl 

 arsenoxides usually produce the former effect, while the pentavalent 

 alkyl and aryl arsonates usually give the latter picture. The concentrations 

 at which they are active are shown in the accompanying tabulation. From 



Arsenoxides Arsonic acids 



(Me)2AsOH (0.08-0.12 milf) MeAsOlOH)^ (1.4 mif) 



(Et)2AsOH (0.08-0.12 mif) w-ButAsOlOH), (0.008 011/) 



(n-But)2AsOH (inactive) 9)-AsO(OH)2 {0A9m3I) 



(p.AsOK (0.03-0.10 mM) 



this work it thus seems that arsenicals may act differently, this being de- 

 pendent on their valency state and substituent groups, and that effects 

 may occur on both the cytoplasm and nucleus. It is unfortunate that 

 monosubstituted phenylarsenoxides were not tested for comparative pur- 

 poses. Fell and Allsopp (1946 a, b) studied the effects of lewisite on tissue 

 cultures and also found both cytoplasmic and nuclear changes. Cell processes 

 contract, surface blebs appear, fat globules fuse into larger droplets, and 

 vacuolization occurs; the nucleus becomes pycnotic and the chromosomes 

 may be clumped into a single mass. The lethal concentration for lewisite 

 oxide is around 0.01-0.02 mM. When the cells are exposed to a sublethal 

 concentration (0.008 mM) of lewisite oxide for 24 hr, recovery occurs on 

 the addition of dimercaprol, indicating that an antimitotic action is not 

 accompanied by irreversible changes. Some differential action was assumed 

 by Haas (1941) in Anodonta eggs, since nuclear damage occurs with 0.15 

 milf arsenite whereas it requires 0.77 mM for cytoplasmic changes. Brock 

 et at. (1939) also interpreted their results on sea urchin eggs as a primary 

 effect of arsenite on the nucleus, but the evidence for this is not apparent. 

 When Euglena is kept for long j^eriods in 1 mikf arsenite, nuclear changes 

 occur, manifested by increased Feulgen staining and coarser granulation 



