1. Ehrlich
ascites-
carcinoma cells contained relatively high concentrations of
spermidine and
spermine, but the
putrescine content of the washed cells was less than 10% of that of higher
polyamines. 2.
Ascites-tumour cells likewise exhibited high activities of L-
ornithine decarboxylase (EC 4.1.1.17),
S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50),
spermidine synthase (EC 2.5.1.16) and
spermine synthase. 3. During the first days after the inoculation, the
polyamine pattern of the
ascites cells was characterized by a high molar ratio of
spermidine to
spermine, which markedly decreased on aging of the cells. 4. Various
diamines injected into mice bearing
ascites cells rapidly and powerfully decreased
ornithine decarboxylase activity in the
carcinoma cells, apparently through a mechanism that was not a direct inhibition of the
enzyme in vitro.
Cadaverine (1,5-diaminopentane) and
1,6-diaminohexane were the most potent inhibitors of
ornithine decarboxylase among the
amines tested. 5. Chronic treatment of the mice with
diamines resulted in a virtually complete disappearance of
ornithine decarboxylase activity, and after 24h a significant decline in
spermidine accumulation. 6.
Cadaverine appeared to be an especially suitable compound for use as an inhibitor of the synthesis of higher
polyamines, at least in Ehrlich
ascites cells, since this
diamine also acted as a competitive inhibitor for
putrescine in the
spermidine synthase reaction without being incorporated into the higher
polyamines.