INHIBITION OF HUMAN NEURO-BLASTOMA DNA-POLYMERASE ACTIVITIES BY PLANT-LECTINS AND TOXINS

The effects of concanavalin A and ricin (RCAII, MW 65,000) [antitumor activity] on [3H]thymidine incorporation into human neuroblastoma IMR-32 DNA showed reduction of total DNA synthesis to 50% and 70% of control, respectively. Two DNA polymerase (DNA nucleotidyltransferase, EC 2.7.7.7) activities (.alpha. and .beta.) involved in the biosynthesis in vitro of DNA were separated by sucrose density gradient centrifugation from IMR-32 cell homogenate. The DNA polymerase .alpha. activity was also purified by selective precipitation with polyethylene glycol (MW 6000) followed by agarose-concanavalin A column chromatography. The activities of both DNA polymerases were examined at various concentrations of mutagenic and nonmutagenic plant agglutinins and the toxin ricin. Concanavalin A and ricin specifically inhibited DNA polymerase .alpha. activity (activity reduced to 19% and 10%, respectively), whereas DNA polymerase .beta. activity was inhibited (reduced to 16%) by red kidney bean agglutinin.