STRUCTURAL REQUIREMENTS OF ANALOGS OF POLYAMINES FOR MIGRATION AND GROWTH OF IEC-6 CELLS

Healing of gastrointestinal mucosal lesions occurs through two process es: an early one involving cell migration and a later one in which cel l division replaces lost cells. Both processes require the presence of polyamines, but the mechanism of action of these compounds is unknown . In the present study, we examined the ability of analogues of spermi dine and spermine to support migration and growth of IEC-6 cells that have been grown in alpha-difluoromethylornithine to inhibit polyamines . All analogues of spermidine with the general formula x-3 (referring to the numbers of carbon atoms on either side of the central nitrogen) , where x = 2-12, competed with spermidine for entry into the cells. H owever, in addition to spermidine (x = 4), only compounds for which x = 2, 3, or 6 supported migration and only those for which x = 2 or 7 s upported growth. Spermine analogues 3-x-3, for which x = 3, 6, 9, or 1 2, competed for entry into the cells, but only compounds for which x = 3 or 6 supported migration and only the compound for which x = 3, in addition to spermine (x = 4), supported growth. In addition, analogues 2-3-2, 3-2-3, and 2-(3)(2), a branched compound, supported both migra tion and growth but entered the cell via a mechanism different than th at for spermidine and spermine. These data define some of the specific structural requirements for polyamines to produce their physiological effects.