GROWTH AND BIOCHEMICAL EFFECTS OF UNSYMMETRICALLY SUBSTITUTED POLYAMINE ANALOGS IN HUMAN LUNG-TUMOR CELLS1

Three unsymmetrically substituted polyamine analogues demonstrate sign ificant and selective antitumor effects. Each of the analogues N-1-eth yl-A(11)-propargyl-4,8-diazaundecane (PENSpm), -1-ethyl-N-11-(cyclobut yl)methyl-4,8-diazaundecane (CBENSpm), and 1-ethyl-N-11-(cyclopropyl)m ethyl-4,8-diazaundecane (CPENSpm) is cytotoxic to a representative non -small-cell lung carcinoma line, NCI H157, while being only growth-inh ibitory to a representative small-cell-lung carcinoma line, NCI H82. C ytotoxicity is accompanied by a significant increase in expression of the polyamine catabolic enzyme spermidine/ spermine N-1-acetyltransfer ase (SSAT) at the levels of activity and steady-state mRNA. These new analogues are significant both for their cell-type-specific activity a nd as synthetic prototypes for the addition of SSAT-activated function al groups.