Effect of local anesthetics on the inhibition of protein synthesis by ricin.

Abstract

In the previous paper, 1) we indicated that local anesthetics such as dibucaine and procaine reduced the toxic action of ricin on Balb/3T3 clone A-31 cells, while these drugs did not show such an effect on KN7-8, a transformed variant of clone A-31. To clarify the different action of the local anesthetics on the cytotoxicity of ricin toward the normal and the transformed cells, some of the possibilities were examined. Dibucaine did not show any influence on the rate of uptake of 125I-ricin into the cells. Furthermore, the rate of reduction of the disulfide bond between the A and B chains, and degradation of ricin in the cells were unaffected by dibucaine. However, the inhibition of the poly U-directed protein synthesizing system from A-31 cells by ricin was reduced in the presence of a low concentration of dibucaine or procaine. Therefore, the most probable explanation for the reduced sensitivity to the toxin in normal cells in the presence of the local anesthetics is that these drugs have some influence on the protein synthesizing system of the normal cells and reduce the inhibitory action of the toxin.