PHYSIOLOGICAL-EFFECTS IN BOVINE LYMPHOCYTES OF INHIBITING POLYAMINE SYNTHESIS WITH ETHYLGLYOXAL BIS(GUANYLHYDRAZONE)

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (11) , 5332-5337
Abstract
Ethylglyoxal bis(guanylhydrazone) is a more specific inhibitor of polyamine biosynthesis than the widely used methylglyoxal bis(guanylhydrazone). The physiological effects on mitogenically activated lymphocytes of polyamine depletion with ethylglyoxal bis(guanylhydrazone) were examined. In the presence of ethylglyoxal bis(guanylhydrazone) and the ornithine decarboxylase inhibitor .alpha.-difluoromethylornithine, the cellular contents of putrescine, spermidine and spermine were decreased by 75-90, 65-80 and 40-60%, respectively, compared with control cultures. Inhibition of DNA synthesis in these polyamine-deficient cells was always greater than that of protein synthesis. Upon addition of spermidine to the deficient cells, the cellular spermidine content was restored within 4 h, but the complete recovery of macromolecular synthesis took 10-20 h. Thymidine kinase and DNA polymerase .alpha. activities in polyamine-deficient cells were lower than those in normal cells, whereas RNA polymerase II and leucyl transfer RNA synthase activities were nearly equal to those in normal cells. Thus, polyamines may regulate the synthesis of specific proteins. Decreased synthesis of replication proteins in polyamine-deficient cells may be 1 reason for the reduced synthesis of DNA.

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