Irreversible inhibition of the early increase in ornithine decarboxylase activity following growth stimulation is required to block Ehrlich ascites tumor cell proliferation in culture

Abstract

Summary Ehrlich ascites tumor cell growth in culture was inhibited by α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, provided that treatment was initiated at the time of growth stimulation. When α-difluoromethylornithine was added after the activation of polyamine synthesis caused by the growth stimulus, i.e. when a 3–5-fold increase in putrescine and spermidine content had occurred, cell proliferation was completely unaffected. α-Methylornithine, a competitive inhibitor of ornithine decarboxylase, did not affect cell proliferation even when added at the time of growth stimulation. Compared to α-difluoromethylornithine, α-methylornithine only produced a partial and transient decrease in the cellular putrescine and spermidine content.