BIS(BENZYL)POLYAMINE ANALOGS ARE SUBSTRATES FOR A MAMMALIAN CELL-TRANSPORT SYSTEM WHICH IS DISTINCT FROM THE POLYAMINE-TRANSPORT SYSTEM

Bis(benzyl)polyamine analogues (e.g. NN'-bis{3-[(phenylmethyl)amino]propyl}-1,8-diamino-octane [C6H5CH2NH-(CH2)3NH(CH2)8NH(CH2)3NHCH2C6H5]) have previously been shown to regulate polyamine biosynthesis and growth of rat hepatoma (HTC) cells. Saturable uptake of the analogues, the ability of other bis(benzyl)polyamine analogues to compete for this uptake and the trans-acceleration of this uptake in pre-loaded cells indicate that these novel compounds are accumulated through the action of a transport system in HTC cells. A mutant Chinese-hamster-ovary (CHO) cell line, CHOMG, which lacks a functional polyamine-transport system, exhibited saturable bis(benzyl)polyamine uptake identical with that observed in the parental CHO cells, which have normal polyamine transport. The uptake of the analogue by both CHOMG and CHO cells was competitively inhibited by other bis(benzyl)polyamine analogues, but was insensitive to excess spermine. Treatment with α-difluoromethylornithine, an inhibitor of polyamine biosynthesis, resulted in the enhancement of spermine uptake in CHO cells but did not alter the uptake of a bis(benzyl)polyamine analogue by either CHO or CHOMG cells. Thus it appears that bis(benzyl)polyamine analogues are substrates for a mammalian-cell-transport system distinct from the polyamine-transport system.