0^2 ANTIMETABOLITES AS MITOTIC POISONS I3 



of the spindle, equatorial constriction in telophase, cytokinesis, and perhaps con- 

 traction of the chromosomal fibers of the spindle in the early anaphasic separation 

 of sister chromosomes. Contraction of the cell models depends on a splitting of 

 ATP, but anaphasic elongation of the stembody of the spindle, which pushes the 

 separating groups of chromosomes even farther apart (Belar, 1929), depends on a 

 plasticizing effect of unsplit ATP or other polyphosphates (Weber, 1955). Spindle- 

 body elongation is thus equivalent to the simple relaxation of most contractile 

 structures. The asters also become larger in anaphase (Hughes and Swann, 1948). 

 The orientation of some of the cell organelles during mitosis can be interpreted 

 as contributing to the provision of polyphosphate to the desired structures in the 

 proper sequence in time and space. Mitochondria, the sites of aerobic ATP pro- 

 duction, assume characteristic positions in some grasshopper cell divisions, lining 

 up in the equatorial cytoplasm outside the spindle and elongating parallel to 

 the spindle axis. Nakahara (1952) has suggested that the mitochondria may 

 participate in induction of the cleavage furrow and has observed their elongation 

 in this region despite inhibition of anaphasic chromosome movement by caffeine 

 or acriflavine. The mitochondria behave abnormally in cells whose cleavage is 

 inhibited by podophyllin components (Momma, 1953) or auramin (Kawamura, 

 1953). Perhaps the mitochondria provide adenosine triphosphate to the equatorial 

 cell cortex, or possibly to a substance responsible for triggering anaphasic move- 

 ment of the chromosomes. 



Material released from the chromosomes in anaphase and staining in a manner 

 similar to ribonucleic acid has occasionally been described. Jacobson and Webb 

 (1952) noted that material presumed to be ribonucleoprotein is released from 

 anaphasic chromosomes into the cytoplasm between the chromosome groups. 

 This material is not released from the chromosomes of metaphases blocked by 

 antifolic acids (Jacobson, 1952). The chromosomes leave a high concentration of 

 ribose nucleoprotein behind them at the equatorial plate after metaphase in the 

 lily (Swift, 1953). Similar observations have been made on living chick fibroblasts 

 in vitro with ultraviolet light (Davies, 1952). This may be the material described 

 as flowing from the kinetochore onto the spindle fibers (Belar, 1929; Kupka and 

 Seelich, 1949). 



Perhaps ribonucleoprotein normally released from anaphasic chromosomes 

 carries adenosine triphosphate, which is involved in contraction of the chromo- 

 somal fibers of the spindle, or polyphosphate groups that serve to relax the stem- 

 body. However, the concept of phosphorylated pentose nucleic acid is uncertain 

 (Brachet, 1955). 



It was suggested by Swann (1952a, 1952b) and by Mitchison (1952) that nu- 

 cleic acid or individual nucleotides might be related to the "structural agents" 

 postulated to be released from chromosomes and to be responsible for the changes 

 in structure of the mitotic apparatus after metaphase, especially for the decrease 

 in birefringence of the spindle as the chromosomes move poleward in anaphase. 

 Mitchison (1952) suggested that when Swann's structural agent reaches the polar 

 cytoplasm of the cell it causes the cell membrane to expand and bubble there, 

 and Boss (1955) has proposed that this membrane activity is caused by ribonucleo- 

 protein released from the chromosomes. 



