84 The Chemistry of the Injured Cell 



these investigations the importance of thio-amino acids seemed 

 fairly established. However, Schwarz (1944) announced that diets 

 had to be simultaneously deficient in both thio-amino acids and in 

 a tocopherol to be effective in inducing massive liver necrosis. 

 Meanwhile an interesting controversy went on between American 

 and British workers about the part played by yeast, the composition 

 of which varies considerably in the two countries. From this dis- 

 pute came the discovery by Schwarz (1951) in ordinary casein and 

 most American yeasts but not in most European yeasts of factor 3, 

 a substance that protected livers against dietary necrosis. It was 

 then found that factor 3 relies largely on its selenium content for 

 its activity (Schwarz and Foltz, 1957) . Cystine likewise may owe 

 its protective property to contamination with selenium and not to 

 any property of the amino acid molecule. Hence dietary liver 

 necrosis develops when there is a simultaneous lack of a tocopherol 

 (vitamin E) and an organic compound of selenium (factor 3) 

 (Schwarz et al., 1959) . The presence of inorganic selenium in the 

 diet is usually sufficient to protect against the necrogenic effects of 

 this deficiency. The necrosis, however, is influenced by other factors 

 such as food intake, environmental temperature, age of the animal, 

 endocrine status and level of dietary fat apart from a tocopherol. 

 It is possible also that the intestinal bacteria may play a part in the 

 initiation of dietary liver necrosis (Gyorgy, Stokes, Goldblatt and 

 Popper, 1951; Beveridge, 1954). 



THE STRUCTURAL CHANGES OF DIETARY NECROSIS 



Dietary liver necrosis takes some time to develop, according to 

 the nature of the deficiency. In some instances rats have shown 

 necrosis after two to three weeks of feeding, in others necrosis takes 

 forty-eight to eighty-eight days to develop. Hence there is a pre- 

 necrotic and necrotic phase. The latter very often kills quickly 

 though sometimes animals survive only to pass into postnecrotic 

 scarring of the liver some months later. 



There are no characteristic cytological disturbances before 

 necrosis appears. Shrinkage of liver cells from loss of cytoplasm, 

 decrease of basophilic (RNA) granules and a steady increase of fat 

 in the centrolobular cells, but no alteration in glycogen content, 



