Cell Damage 79 



Triethyl Tin Compounds 



Alkyl tin compounds are used a great deal in the plastics in- 

 dustry and have been suggested as fungicides. Most tin compounds 

 are insoluble in the body fluids and so are harmless. Many of the 

 alkyl derivatives are soluble and toxic, especially triethyl com- 

 pounds. The triethyl derivatives give paresis, tremors and convul- 

 sions in animals and induce a striking interstitial oedema of the 

 white matter of the brain and spinal cord of the rat without ob- 

 viously damaging the neurones. In vitro they interfere with oxida- 

 tive phosphorylation by mitochondria (Aldridge and Cremer, 

 1955) but the relationship of this finding to the in vivo effects is 

 far from certain. The toxic action of triethyl tin compounds can 

 be forestalled by premedication with dimercaprol (BAL) which 

 suggests that they may exert their effect by inhibiting a thio-enzyme 

 (see also Lewisite) . 



Bacterial Toxins 



Diphtheria toxin has so far defied all attempts to discover the 

 nature of its biochemical lesion. When given in large doses to 

 susceptible animals a long latent period of many hours intervenes 

 in which no morphological or biochemical disturbances can be 

 demonstrated. Such arresting features of intoxication as increased 

 resistance of the animal to insulin, reduced capacity to synthesise 

 carbohydrates or to metabolise lactic acid, (Popjak, 1948) with 

 decrease in the stores of muscle phosphocreatine and increased water 

 content of cells are all secondary effects that appear many hours 

 after a primary injury that baffles the investigator (Holmes, 1939). 

 Perhaps there is competitive inhibition or block of synthesis of the 

 cytochromes in the diphtheritic animal. The succinoxidase system 

 appears to be susceptible to diphtheria toxin (Pappenheimer and 

 Williams, 1952) . Recent studies with stabilised growing HeLa 

 cells show that the toxin is rapidly adsorbed and quickly inhibits 

 protein synthesis. Anaerobic respiration or glycolysis remains un- 

 affected but some inhibition of succinoxidase is induced (Strauss 

 and Hendee, 1959) . 



Clostridium welchii toxins produce severe necrosis of muscle 

 with liberation of gas. They constitute a group of toxic proteins, 



