Cell Damage 77 



mide. Along with the calcium accumulation there is an increase of 

 intracellular sodium and a decrease in potassium and magnesium. 

 These ionic changes may well be the outcome of loss of semiperme- 

 ability of the cell wall referable to an action there of thioacetamide 

 and this idea of Gallagher et al. is certainly supported by their 

 demonstration that the antihistamine, Phenergan, gives consider- 

 able protection against thioacetamide necrosis. This phenomenon, 

 however, has no apparent connection with histamine release for 

 thioacetamide itself does not release histamine from cells. The re- 

 cent investigations of Judah (1960) suggest that the antihistamines 

 inhibit some fundamental mechanism governing water and elec- 

 trolyte movements by which mitochondria both swell and contract. 



Heliotrine 



Alkaloids with a pyrrolizidine ring occur in plants from the 

 genera Senecio and Erectites (Compositae) , Crotolaria (Legumino- 

 sae) and Heliotropium (Boraginaceae) . Four of these alkaloids, 

 retrorsine, isatidine, lasiocarpine and heliotrine cause liver necrosis 

 in animals (Selzer et al., 1951; Schoental et al., 1954; Bull et al., 

 1958) . Heliotrine inhibits the DPN-dependent respiratory enzymes 

 in liver cells and mitochondria. This occurs just when liver cell 

 necrosis is becoming extensive, sometimes as early as one hour after 

 exposure to heliotrine. Miss Margot J. Bailie (Thesis, 1959) , work- 

 ing with Christie in E. J. King's laboratory at Melbourne, Australia, 

 has shown that heliotrine picks out oxidative metabolism rather 

 than the phosphorylation system while liver cells are necrosing. 

 Only at a later stage, when necrosis is widespread, and DPN is 

 partly successful in re-activating DPN-linked oxidation, is un- 

 coupling of phosphorylation evident. 



Dimethylnitrosamine 



This compound destroys the centrolobular liver cells when 

 given to laboratory animals by various routes (Barnes and Magee, 

 1954) . It is quickly metabolised in the liver both in vitro and in 

 vivo (Magee and Vandehar, 1958). During the early stages of 

 poisoning the incorporation of C 14 labelled amino acids into rat 

 liver proteins is greatly reduced (Magee and Vandehar, 1958) so 



