ANTILEUKEMIC EFFECTS OF NONMETABOLIZABLE DERIVATIVES OF SPERMIDINE AND SPERMINE

To determine whether non-metabolizable derivatives of spermidine and s permine exert anticancer effects, L1210 leukemic mice were treated wit h 5,8-dimethylspermidine and 5,8-dimethylspermine. Both derivatives cu red 5% of the leukemic mice. The increase in median survival time, how ever, was slight. In combination with alpha-difluoromethylornithine (D FMO), an ornithine decarboxylase inhibitor, only 5,8-dimethylspermine had a favorable effect. Treatment with DFMO is known to increase the u ptake of extracellular polyamines and presumably their derivatives, by depleting the intracellular putrescine and spermidine content. Howeve r, treatment of L1210 leukemia cells in vitro with DFMO did not affect the uptake of the methyl-substituted polyamines added to the growth m edium. 5,8-Dimethylspermidine and 5,8-dimethylspermine repressed the o rnithine decarboxylase activity when added to cultures of L1210 leukem ia cells. S-Adenosylmethionine decarboxylase activity was only repress ed by 5,8-dimethylspermine. This finding may explain the potentiation by this derivative and not by 5,8-dimethylspermidine, of the antileuke mic effect of DFMO.