Acquired Resistance of Liver Cells to the Toxic Action of Uranium Nitrate. ∗

A statement has been made previously concerning the type, distribution and severity of the injury to the liver by the use through subcutaneous injection of a solution of uranium nitrate. 1 , 2 In addition, observations were recorded 2 concerning the types of repair processes developing in the liver as a result of the reaction of the liver to this hepatoxic agent, and the resistance or lack of resistance which such processes manifested when the liver was subjected to the toxic action of chloroform, administered by inhalation.

The present series of experiments are concerned with the injury induced to hepatic epithelium by the subcutaneous use of uranium nitrate in the amount of either 2 or 4 mg. per kilogram, the type of repair process which is inaugurated by such injuries and the resistance which certain cells in such areas of repair may acquire to secondary intoxications by uranium. During the course of the experiments biopsy material has been obtained from the liver for cytological study and at such periods tests of hepatic function have been made by the use of phenoltetrachlorphthalein according to the technique devised by Rosenthal. 3

Sixty-three dogs have been used in the experiments. Twentynine of the dogs were intoxicated with 2 mg. of uranium nitrate per kilogram. Ten of the animals failed to survive the intoxication. In the remaining 19 dogs there was an initial increase in the plasma concentration of phenoltetrachlorphthalein at the height of the intoxication which did not exceed 18%. In 8 of these animals the plasma was free from the dye in half an hour. In the remaining 11 dogs the removal of the dye was delayed. Biopsy material removed from the livers of such animals showed an increase in stainable lipoid material in the hepatic epithelium, and edema, but rarely vacuolation or necrosis of the cells.