AMINOOXY ANALOGS OF SPERMIDINE EVIDENCE THE DIVERGENT ROLES OF THE CHARGED AMINO NITROGENS IN THE CELLULAR PHYSIOLOGY OF SPERMIDINE

Two recently devised spermidine analogues, N-[2-aminooxyethyl]-1,4-dia minobutane (AOEPU) and 1-aminooxy-3-N-[3-aminopropyl]-aminopropane (AP APA), were used to elucidate the role of charge distribution in the fu nctions of spermidine in cultured baby hamster kidney cells. The drugs did not affect cell proliferation nor did they relieve the growth-arr est but potentiated the metabolic disturbances caused by DL-alpha-difl uorbmethylornithine (DFMO). Neither drug affected spermidine uptake bu t both competed with putrescine uptake. Neither drug could replace spe rmidine in the control of S-adenosylmethionine decarboxylase and accum ulation of the reaction product. APAPA prevented spermine synthesis an d showed that modest putrescine synthesis take place in the presence o f DFMO. AOEPU, but not APAPA, interfered with cellular constituents re sulting in. enzymatic formation, accumulation and excretion to culture medium of UV-absorbing catabolites.