Polyamine analog bis(ethylamino)-5,10,15-triazanonadecane (BE-4-4-4-4) enhances simian virus 40 late gene expression

Purpose: The polyamine analog bis(ethylamino)-5, 10,15-triazanonadecane (BE -4-4-4-4) depletes cellular polyamines and inhibits malignant cell growth. We have previously shown that BE-4-4-4-4 inhibits nucleosome condensation o n supercoiled DNA in a cell-free system. Here we sought to determine whethe r BE-4-4-4-4 inhibits nucleosome condensation in cells, and whether that ef fect alters the expression of specific genes. Methods: We used the simian v irus 40 (SV-40) minichromosome as a model system and studied the expression of the viral late genes. It is known that the SV-40 late genes are regulat ed by the steroid receptor elements that, in turn, control gene expression by altering nucleosomal organization. Results: We observed a more than six fold increase in SV-40 late gene expression in cells pretreated with BE-4-4 -4-4 for 18 h. The polyamine analog bisethyl norspermine (BE-3-3-3), that d oes not affect nucleosomal condensation in cell free systems and has little effect on chromatin structure in cultured human tumor cells, had a negligi ble effect on SV-40 late gene expression under treatment conditions identic al to those used with BE-4-4-4-4. Conclusion: Similar to the findings in th e cell-free system, the polyamine analog BE-4-4-4-4 inhibited nucleosome fo rmation and, thereby, altered the expression of specific genes in a cellula r system.