INHIBITION OF PREREPLICATIVE POLYAMINE ACCUMULATION IN REGENERATING RAT-LIVER

Injections of 1,3-diaminopropane, an inhibitor of mammalian ornithine decarboxylase (EC 4.1.1.17) in vivo, during the first 10 h after partial hepatectomy markedly delayed stimulation of liver DNA synthesis from 3H-thymidine normally occurring at the beginning of the 2nd day of liver regeneration. Inhibition of ornithine decarboxylase by repeated injections (every 2 h) of diaminopropane for 10 h after partial hepatectomy abolished enhancement in DNA synthesis at 20 h postoperatively, where shorter periods of postoperative diaminopropane treatment resulted in less complete prevention of DNA synthesis. Under these experimental conditions the rate of liver DNA synthesis in vivo from 3H-thymidine showed a highly significant positive correlation with the concentration of tissue spermidine but not with that of putrescine or spermine. It was possible to prevent accumulation of spermidine and to depress liver DNA synthesis at 24 h postoperatively by starting treatment with diaminopropane after varying lag periods following partial hepatectomy. Treatment with diaminopropane started as late as at 12 h after partial hepatectomy still prevented any accumulation of liver spermidine and resulted in a profound inhibition (about 85%) of DNA synthesis at 24 h postoperatively. Inhibition of DNA synthesis was gradually subsiding when commencement of amine treatment was moved farther from the time of operation.