124 



ADGG had an ID = 3 x 10 M. ADGG is somewhat less toxic 

 than a-amanitin which may be a consequence of its lower 

 affinity for RNA polymerase II or of permeability dif- 

 ferences. Both compounds are clearly toxic to the cells 

 with long exposure times which implies that entry to the 

 cell is restricted. The Con A portion of the ADGG-Con A 

 conjugate appears to be providing facilitated entry of the 

 conjugate to allow for the observed cytotoxicity with only 

 15 minutes of exposure. 



The effects of a-amanitin and ADGG over 48 hours of 

 incubation with H-7Wcr cells are presented in Table 8. As 

 was found with H-7 cells, ADGG was less toxic than free a- 



amanitin with an ID sn of 1.9 x 10 M in comparison to 6.4 x 



_7 

 10 M for a-amanitin. These values are essentxally the 



same as those for the parent cell line, H-7. The effects 

 of conjugated ADGG were examined with the H-7Wcr in an 

 attempt to explore the mechanism of ADGG-Con A toxicity. 

 H-7Wcr cells are resistant to the toxic effects of Con A 

 exposure but the mechanism of their resistance is not known. 

 Although they bind Con A as well as the parent line, it 

 was thought that the H-7Wcr may not internalize the bound 

 lectin. Exposure of H-7Wcr to different concentrations of 

 ADGG-Con A, Con A, ADGG and a-amanitin for 15 minutes 

 resulted in the inhibition shown in Table 9. As was ex- 

 pected, Con A had minimal toxic effect on the cells up to 



160yg/ml where 9% inhibition was seen. ADGG-Con A, however, 



-7 

 was very toxic with an ID CA of 3.5 x 10 M, comparable to 



