EFFECT OF POLYAMINE ANALOGS AND INHIBITION OF POLYAMINE OXIDASE ON SPERMIDINE SPERMINE N'-ACETYLTRANSFERASE ACTIVITY AND CELL-PROLIFERATION

Several bis(ethyl)polyamine analogues are currently undergoing trials as antitumor agents. The ability of some of these analogues to induce spermidine/spermine N-1-acetyltransferase and to inhibit cell prolifer ation was examined in a number of different cell lines. Although N-1, N-11 bis(ethyl)norspermine was a potent inducer of the acetylase in al l cell lines tested, there was a striking difference in the acetylase induction in response to N,N'-bis(ethylamino)propyl]- 1,7-heptanediami ne. This was a very strong inducer in CHO cells but had no effect in H T29 cells and very little effect in COS-7 or L1210 cells. There was no correlation between the induction of the acetylase and the ability of these analogues to inhibit cell proliferation since N',N-11-bis(ethyl amino)-propyl]-1,7-heptanediamine was as at least as strongly antiprol iferative as N-1,N-11-bis(ethyl)-norspermine or N',N-12-bis(ethyl)sper mine. Acetylase induction and the intracellular level of the analogues were increased in CHO cells by treatment with a polyamine oxidase inh ibitor suggesting that they are degraded by polyamine oxidase, The abs ence of polyamine oxidase in some tumors may therefore contribute to t heir sensitivity to these analogues.