Effect of DL-alpha-hydrazino-delta-aminovaleric acid, an inhibitor of ornithine decarboxylase, on polyamine metabolism and growth of mouse sarcoma-180

Gan. 1976 Aug;67(4):569-76.

Abstract

DL-alpha-Hydrazino-delta-aminovaleric acid (DL-HAVA) is a potent and fairly specific inhibitor of ornithine decarboxylase (EC 4.1.1.17). Its effect on polyamine metabolism and cell proliferation was investigated in sarcoma-180, inoculated into the axillary region of mice. In the tumor tissues, the activities of ornithine and S-adenosyl-L-methionine decarboxylases and the putrescine level were much higher in the early stage of growth than those in normal mouse liver. Administration of DL-HAVA greatly depressed the putrescine level and putrescine formation from L-ornithine. It also suppressed DNA synthesis and increase in weight of the tumor tissue. However, it had little effect on RNA synthesis or the tissue concentration of spermidine and spermine. The inhibition of DNA synthesis and subsequent tumor development by DL-HAVA was effectively prevented by putrescine, but not by cadaverine or 1,7-diaminoheptane. From these results it is concluded that the suppression of DNA synthesis and neoplastic growth by DL-HAVA is due to decrease in the putrescine level by inhibition of ornithine decarboxylase.

MeSH terms

  • Adenosylmethionine Decarboxylase / antagonists & inhibitors
  • Animals
  • Carboxy-Lyases / antagonists & inhibitors*
  • Cell Division / drug effects
  • DNA, Neoplasm / biosynthesis
  • Depression, Chemical
  • Hydrazines / pharmacology*
  • Liver / enzymology
  • Male
  • Mice
  • Ornithine / analogs & derivatives
  • Ornithine Decarboxylase Inhibitors*
  • Polyamines / biosynthesis*
  • Putrescine / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Sarcoma 180 / metabolism*
  • Spermidine / biosynthesis
  • Spermine / biosynthesis
  • Valine / analogs & derivatives*
  • Valine / pharmacology

Substances

  • DNA, Neoplasm
  • Hydrazines
  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • RNA, Neoplasm
  • Spermine
  • alpha-hydrazinoornithine
  • Ornithine
  • Carboxy-Lyases
  • Adenosylmethionine Decarboxylase
  • Valine
  • Spermidine
  • Putrescine