EFFECTS OBSERVED IN THE WHOLE ANIMAL 251 



The intestinal mucosa is often damaged by substances which depress cell 

 growth and mitosis (e.g., the antitumor drugs), so it is not surprising that 

 effects from iodoacetate administration have been observed. Laszt and Ver- 

 zar (1936) found a striking enlargement of the whole gastrointestinal tract 

 in poisoned rats at 34 days, both stomach and intestine being essentially 

 doubled in weight. The injection of high doses (60-200 mg/kg) of iodoace- 

 tate in rats causes jiyloric spasm, hemorrhagic enteritis, and gross patholo- 

 gical changes in the intestine (KHnghoffer, 1938). The intestine shows spastic 

 contractions, increased mucus secretion, and microscopic damage to the 

 epithelium and villi (Ohnell and Hober, 1939). Giving rats water which is 

 2.7-5.4 mM in iodoacetamide leads to gastritis and gastric ulcers, although 

 iodoacetate does^not do this, perhaps due to permeability differences (one 

 might expect the low gastric pH to favor iodoacetate penetration, however). 

 Another effect of iodoacetate on the intestine may or may not be related to 

 this damage; this is the inhibition of fat absorption, which is very marked 

 (Verzar and Laszt, 1934.) and may lead to steatorrhea (Laszt and Verzar, 

 1935). Laszt and Verzar (1936) postulated a relationship between this state 

 and coeliac disease (intestinal infantilism, Gee-Hertersche Kranlheit), since 

 the symptoms are similar and both are relieved by the administration of 

 yeast, but whether this involves adrenal dysfunction, abnormalities in in- 

 testinal absorption, vitamin deficiencies, or something else, is not known. 



Renal damage may be caused by higher doses of iodoacetate; this may 

 be due not to a special sensitivity but to exposure to a higher concentra- 

 tion of inhibitor than most tissues. The most obvious effect is a necrosis 

 of the convoluted tubules (Stevenson and White, 1940), characterized by 

 cellular fragility, occlusion of the tubules, vacuolization of the tubular cells, 

 and dilatation of the vessels (Becker and Rieken, 1954). Other effects ob- 

 served but not studied extensively are the osteoporosis, which could well 

 be due to inadequate intestinal absorption of calcium (Laszt and Verzar, 

 1935), but there is evidence that deposition of calcium may also be disturb- 

 ed (Verzar and Laskowski, 1937); adrenal cortical hypertrophy (Laszt and 

 Verzar, 1936) with simultaneous reduction in hormone levels (Giroud et al., 

 1941); and a generalized edema of animals (Hikiji, 1932). The total excre- 

 tion of Na+ and K+ by rats is decreased by 25 mg/kg iodoacetate intraperi- 

 toneally; during the first day the Na+ excretion drops from 36.5 to 9 mg/kg 

 body weight, and the K+ from 146 to 116 mg/kg body weight, but on suc- 

 ceeding days the excretion returns to normal (Boccacci and Quintiliani, 

 1960). This is due mainly to the intestinal stasis and reduction in fecal 

 outi)ut. 



Toxic and Lethal Doses 



A collection of data on toxic and lethal doses is given in Table 1-39, from 

 which no obvious species differences are evident. The LD50 is usually SO- 

 SO mg/kg, corresponding to 0.27-0.4 millimole/kg of iodoacetate. Bromo- 



