66 



mean cell size has occurred as a result of exposure to 

 either inhibitor which might have occurred in a growing 

 but nondividing population of cells or in one that was 

 dividing in the absence of DNA synthesis. 



Differential uptake of ADH-BSA could possibly occur 

 by means of receptor mediated uptake or enhanced pinocyto- 

 tic uptake by susceptible cells. In order to explore the 



latter possibility, AV3 , CHO and EL4 cells were examined for 



125 

 their relative rates of pinocytosis. Uptake of I labeled 



BSA over a 24 hour period was used as a measure of pinocyto- 

 sis (Steinman et al., 1974). Table 4 presents a summary 

 of the pinocytosis rates in comparison to the molar concen- 

 trations of free versus conjugated u-amanitin required for 

 25% inhibition of cell growth and H-TdR incorporation for 

 all three cell lines. The amount of pinocytosis observed 

 with each cell line was in direct correlation to the rela- 

 tive sensitivity of the cell line to conjugated a-amanitin. 



AV3 cells were 3.5 times more active in the pinocytic uptake 



125 

 of I-BSA than were CHO cells, whereas EL4 cells took up 



negligible amounts under similar conditions. These data 

 indicate that the increased sensitivity of AV3 cells to 

 conjugated a-amanitin is a direct function of increased 

 pinocytotic uptake of the conjugate relative to the other 

 cell lines tested. 



The results of the ADH-BSA experiments pointed out the 

 necessity for using a macromolecular carrier for which spe- 

 cific cellular receptors are known to exist to further 



