EFFECTS ON MITOSIS AND GROWTH 323 



at least a depletion of the low molecular weight thiols of the cells. Possibly 

 maleate is antimitotic only after reaction with cellular thiols, or is split 

 off from the thiols within the cells and then reacts with some component 

 involved in mitosis, since these tests were run over a period of 24 hr. Fur- 

 ther argument against the SH reaction theory is the fact that chloromaleate 

 and chloromaleimide react readily with SH groups but are not antimitotic 

 (Friedmann et al, 1952 a). One might explain this by assuming that the 

 high reactivity of these compounds (chloromaleimide reacts completely 

 with glutathione within 1 min) brings about their immediate inactivation 

 in the cells, the addition products with thiols here being mitotically inactive, 

 as are some of the addition products with the l,4-na])hthoquinones, but 

 one would like some experimental evidence for this. Furthermore, chloro- 

 fumarate does not react with thiols and yet is moderately antimitotic. 



These potent antimitotic effects on tissue culture cells are not seen with 

 microorganisms. Thus the growth of the fungi Botrytis allii, Fusarium 

 graminearum, and Penicillium digitatum is not inhibited by maleate at con- 

 centrations of 3.4-8.6 mM (McGowan et al., 1948), and the minimal bac- 

 teriostatic concentrations for Aerobacter aerogenes and Pseudomonas fluo- 

 rescens are 6.9 mM and 2.5 mM respectively (Cooper and Goddard, 1957). 

 The growth of Staphylococcus aureus and E. coli is not inhibited by 0.84 

 mM maleate, but maleimide inhibits 50% at 0.011-0.014 mM, indicating 

 that failure of maleate to penetrate into the bacteria might be responsible 

 for its lack of activity (Marrian et al, 1953). The growth of yeast is also 

 very little affected by maleate up to 1 mM (Kiga et al, 1955). The only 

 detailed study of the effects of maleate on bacterial growth is that of Ni- 

 colle and Joyeux (1950, 1951). The concentration-inhibition curve for E. 

 coli grown on glucose medium is shown in Fig, 2-3, and it is seen that 

 depression of growth becomes marked only above 30 mM. Maleate is more 

 inhibitory when fumarate is the sole carbon source. One must conclude 

 that bacterial and fungal proliferation does not depend on the same factors 

 as mitosis in fibroblasts. 



The investigation of the effects of maleate on plant growth is complicated 

 by the ability of many plant tissues to utilize maleate in their metabolism 

 (see page 312), and stimulation of growth has often been observed. Maleate 

 produces a small but definite stimulation in the bean test for wound hor- 

 mones (English et al, 1939), increases oat coleoptile extension at 1-5 mM 

 (Albaum and Eichel, 1943), and augments the growth of bean and tomato 

 plants following dipping in 15 mM solutions (Greulach, 1953). No effect 

 by maleate has occasionally been reported, as with wheat roots (Lunde- 

 gardh, 1944) and soybean seedlings (Parups et al, 1962) (slight depression 

 noted at 10-50 mM in the latter case). Certainly plant growth does not seem 

 to be sensitive to maleate, and this cannot be entirely explained by failure 

 to penetrate. 



