Cell Damage 73 



stances as chlorpromazine, carbon tetrachloride, tri-ethyl-tin sul- 

 phate, bacterial toxins, thyroxin, heliotrine alkaloids and dime- 

 thylnitrosamine. However, we must be cautious in our statements 

 since this is a field of investigation that is going on actively all 

 the time and the conclusions may need revision as new facts are 

 discovered. 



Carbon Tetrachloride 



Carbon tetrachloride has long been known to damage and kill 

 the cells of the liver, kidneys and to a lesser extent of the heart 

 muscle and brain when administered to animals and man by various 

 routes. Most attention has been centered upon the liver where those 

 effects are very vivid. Within twelve to twenty-four hours of giving 

 a single toxic dose of carbon tetrachloride many of the liver cells 

 congregated around the centrilobular veins develop large vacuoles, 

 undergo fatty degeneration and die. This is followed by rapid mito- 

 tic proliferation of surviving cells and recovery in four to five days 

 in the case of small animals. Clinical experience has made us 

 familiar with similar disturbances of the liver in man but the renal 

 cells are just as often or even more seriously damaged (Cameron 

 and Karunaratne, 1936) . Cytological changes are seen even within 

 an hour or less of exposure to the poison. These show up as loss of 

 the cytoplasmic basophilic bodies and glycogen with accumulation 

 of lipids, but they are most likely a non-specific reaction of the cell 

 to the poison for they are induced by a host of agents and even occur 

 when the animal is starved of protein. 



For some time now, pathologists have suspected that the mito- 

 chondria might be a major site of CC1 4 damage. The first con- 

 vincing proof of this impression came when Christie and Judah 

 (1954) isolated from homogenates of rat's liver poisoned by CC1 4 

 the typical "vacuoles" and showed them to be distorted, swollen 

 mitochondria. Christie and Judah also showed that the oxidation 

 of a number of Krebs cycle intermediates and of octanoate, pyruvate 

 and glutamate by liver mitochondria was inhibited ten to fifteen 

 hours after giving rats CC1 4 . This effect could always be reversed 

 except in the case of octanoate, by the addition of DPN. Similar 

 upsets could be demonstrated in vitro. This suggested that CC1 4 



