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1. 1. Oxidized spermine, an iminodialdehyde, obtained by the enzymic oxidation of spermine, forms complexes with deoxynucleotides, deoxynucleosides, purine bases and synthetic polyribonucleotides. 2. 2. The interaction of oxidized spermine with deoxynucleotides and deoxynucleosides has been demonstrated by spectrophotometric studies. The hyperchromic changes obtained are proportional to the amount of oxidized spermine added and are maximal with guanosine and guanosine 5′-phosphate. 3. 3. Electrophoretic studies indicate that guanine, cytosine and adenine, but not uracil, bind oxidized spermine. 4. 4. The transition from the coiled to the helical structure of polyriboadenylic acid is prevented by oxidized spermine. 5. 5. Complexes between polyribouridylic and polyriboadenylic acid are stabilized by oxidized spermine; the strands do not separate under acid conditions. Hydrogen bonding between complementary polyribonucleotide chains is prevented by pre-incubating the double-stranded structure with oxidized spermine. 6. 6. The binding of oxidized spermine to DNA decreases after deaminating the purine and pyrimidine bases. It has been concluded that the amino groups of the bases are responsible for the irreversible binding of oxidized spermine. The bases bind oxidized spermine in the decreasing order of reactivity: guanine, cytosine, adenine, thymine.

1. The effects of oxidized spermine on the biological activity of Bacillus subtilis DNA were studied by examining the transforming capacity of purified DNA treated in vitro, and of DNA spontaneously released from cells treated with oxidized spermine. 2. Transformation to tryptophan, histidine and methionine independence was affected significantly. The histidine marker was more sensitive to inactivation by oxidized spermine than the linked tryptophan and unlinked methionine markers. 3. NaCl, at high concentrations, antagonized the inhibitory effect of oxidized spermine, indicating the involvement of ionic factors in the binding of oxidized spermine to the DNA. 4. Transforming DNA after treatment with oxidized spermine, was more resistant to heating at 100° than untreated DNA, suggesting interstrand cross-linking.

Spermine, after oxidation by highly purified serum amine oxidase (amine: O2 oxidoreductase (deaminating)), inhibited the multiplication of Ehrlich ascites cells. The oxidation product, oxidized spermine, was separated from the amine oxidase by gel filtration and its toxicity verified. The related triamines, spermidine and diaminodipropylamine, were also oxidized by purified serum amine oxidase, giving rise to cytotoxic products. The polyamines in the absence of amine oxidase did not affect the multiplication of the Ehrlich ascites cells, whereas purified amine oxidase alone exhibited a slight cytotoxic effect. Oxidized [14C]spermine was rapidly taken up by Ehrlich ascites cells on incubation at 37°. The incorporation of radioactive valine, thymidine or uracil, into the corresponding cellular macromolecules, was markedly reduced after treating Ehrlich ascites cells with oxidized spermine for 30 min at 37°.

1. 1. Oxidized spermine, an iminodialdehyde, obtained by the enzymic oxidation of spermine, inhibits the incorporation of labeled thymidine, and uracil into the nucleic acids of growing Escherichia coli cells. The incorporation of labeled valine into bacterial proteins is arrested only after a definite lag period. 2. 2. Oxidized spermine also inhibits nucleic acid synthesis in cell-free systems, using purified DNA-dependent RNA polymerase and DNA polymerase. The inhibition of DNA synthesis by oxidized spermine, is somewhat greater than that of RNA synthesis. 3. 3. The inhibition of nucleic acid synthesis is due to the binding of oxidized spermine to the DNA primer and not to its interaction with the nucleoside triphosphates or the enzymes. 4. 4. Inhibition of DNA replication by oxidized spermine is dependent on the nature of the DNA used and is higher when guanine-cytosine-rich primers are used.