Cell Division 



117 



ber of colchicine derivatives and other alka- 

 loids in search for the molecvilar structure 

 responsible for the colchicine effect. He 

 found that the stilbylamine group is es- 

 sential, though the type of substitution too 

 is important. It is not yet clear how col- 

 chicine acts on the spindle micelles. Lettre 

 suggested that it interferes v^^ith the utiliza- 

 tion of ATP for spindle contraction, since 

 ATP counteracts colchicine. However, there 

 is more to it than inhibition of contraction, 

 since the structure of the spindle and asters 

 is actually destroyed. 



Ostergren ('44) made a comparative study 

 of many chemically imrelated substances 

 that have a colchicine-like action. He called 

 attention to the fact that the more lipoid- 

 soluble the substance the lower the threshold 

 concentration for colchicine-like effect (C- 

 mitosis). He proposed a protein chain folding 

 theory according to which the active mole- 

 cule attracts the lipoid side chains of the 

 proteins, causing a folding up which would 

 explain the breakdown of the cytoplasmic 

 gels and spindle and perhaps also the more 

 than normal shortening of the chromosomes 

 typical of colchicine-mitosis. 



Colchicine destroys the spindle almost 

 universally in both animals and plants. It is 

 very interesting that there are cells and 

 organisms that are resistant to it. In the 

 hamster colchicine is without effect (Orsini 

 and Pansky, '52) and Lettre ('52) has found 

 a strain of ascites tumor in the movise that 

 is resistant. 



Another group of spindle poisons have in 

 common that they combine specifically with 

 — SH groups. Quinones were discovered by 

 Lehmann ('51) to affect specifically spindle 

 and cytokinesis. Organometallic compounds 

 were studied by Klages and Lettre (for ref- 

 erences see Lettre, '51). Their action is re- 

 versed by cysteine and other — SH com- 

 pounds. Chloroacetophenone, another — SH 

 poison, blocks metaphase in vitro (Hughes, 

 '50) and in vivo (Beatty, '51). Sulfhydryl 

 poisons can block mitosis in two ways, either 

 by inhibition of — SH enzymes (Barron, '51) 

 or by combining with - — SH groups of the 

 proteins in spindle and asters and thus in- 

 terfering with the formation and function 

 of these gel strvictures. It is interesting that 

 some — SH poisons are spindle poisons in 

 low concentrations and inhibitors of ante- 

 phase in higher concentration, possibly by 

 interfering with carbohydrate metabolism 

 (Meier and Allgower, '45; Hughes, '50). 



Folic acid, as mentioned above, is essential 

 in antephase and aminopterin prevents cells 



from entering prophase. Hughes ('50) and 

 Jacobson ('51) found that aminopterin and 

 amethopterin block mitosis also at metaphase. 

 Folic acid is thus necessary also for ana- 

 phase movements of chromosomes, but noth- 

 ing is known about how it functions here. 



MODIFICATION OF MITOSIS 



The division of cells involves a complex 

 series of events that normally follow each 

 other in a definite order. It can be inter- 

 rupted experimentally by a variety of in- 

 hibitors that affect one or several links in 

 the chain. Often it is modified in connection 

 with specializations in the growth and func- 

 tion of tissues or in the life cycle of the 

 organism. Thus the mitotic chain may be 

 broken at one point or the other, or the nor- 

 mal sequence of events is changed, or one 

 of the components is altered in some way. 



Completion of cytoplasmic division is most 

 easily affected and so we find many exam- 

 ples of division without cytokinesis. In mam- 

 malian tissues, for instance, binucleate cells 

 are common, and they are the result of such 

 failure of cytoplasmic division (Beams and 

 King, '42). In spermatogenesis of coccids cell 

 division is omitted regularly in the second 

 meiotic division (Hughes-Schrader, '48). If 

 mitosis is interrupted at an earlier point chro- 

 mosome movements and therefore nuclear 

 division are absent. Reproduction of nuclear 

 elements that is not followed by chromo- 

 some movements and cytoplasmic division 

 has been called "endomitosis" (cf. Geitler, 

 '48). Endomitosis may occur with a typical 

 prophase, including increase in nuclear vol- 

 ume and chromosome spiralization. The nu- 

 clear membrane, however, pei'sists and the 

 cell becomes polyploid (somatic tissues of 

 Hemiptera and many other insects). Poly- 

 ploid cells may later again divide by reg- 

 ular mitosis. In other cases prophase is 

 suppressed too, only antephase is left, and 

 there is no visible change in the structure 

 of the interphase nucleus. Where chromo- 

 some reprodiiction is not followed by chro- 

 mosome splitting and separation of chro- 

 matids, endomitosis does not change the num- 

 ber of chromosomes but increases the number 

 of units in each chi'omosome, giving rise to 

 polytene chromosomes. They are best known 

 from larval tissues of Diptera, where through 

 many consecutive endomitoses the nvimber of 

 chromonemata per chromosome may increase 

 a hundredfold. 



The volumes of polytene and polyploid 

 nuclei are usually multiples of the original 



