324 



2. MALE ATE 



The growth of rats is not markedly affected by maleate. Dye et al. (1944) 

 injected doses increasing from 0.5 to 2 mg into young rats for 4 weeks and 

 found the body weight to be about 13% less than in the controls, while 

 Fitzhugh and Nelson (1947) observed growth inhibition in rats over a year 

 when maleate was incorporated at 1-1.5% in the diet. Nothing has been 

 done on the growth of specific proliferating tissues. The marked antimitotic 

 effect in cell cultures brings up the question whether maleate is tumoristatic. 



Fig. 2-3. Effect of maleate on the growth of E. coli 



with glucose as the substrate. (From NicoUe and 



Joyeux, 1950.) 



Boyland (1940) found that the administration of 15 mg/day of maleic acid 

 to mice bearing grafted sarcomata and spontaneous carcinomata led to a 

 slight inhibition of tumor growth, the effects being much less than with 

 malonate. Brunschwig et al. (1946) reported very similar results in rats 

 bearing Walker carcino-sarcomata, 300 mg/kg/day for 15 days producing 

 44% inhibition of tumor growth. There is thus little evidence that maleate 

 is an effective agent in suppressing tumor growth. 



MALEAMATE, MALEIMIDE, AND MALEURATE 



If the mechanism by which maleate produces some of its metabolic and 

 mitotic effects is through reaction with SH groups, one might expect that 

 chemical changes in the carboxylate groups would not abolish the activity, 

 as it does in the case of malonate which interacts by means of its carboxy- 



