Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation.

Serum polyamine oxidase (EC 1.4.3.4) is known to react in vitro with radio-labelled spermine4+ to produce di-oxidized spermine which must incorporate the label. Di-oxidized spermine was compatible with a radio-labelled compound2+ separated from the reaction mixture by ion-exchange chromatography. The compound was measured and had a half-life of about 2.3 h in tissue culture medium. It also rapidly and tightly bound to an unidentified serum component (gel-filtration chromatography indicated a complex of mol. wt 70,000) so that dissociation required treatment with strong acid (10N HCl). Findings suggest that the di-oxidized spermine, in either its free cationic or bound form, potently arrested cell proliferation. This arrest was non-cytotoxic and was confined to the G1 phase of the cell cycle. Products of di-oxidized spermine autodegradation, including trace amounts of stable and cytotoxic acrolein (arrested S phase), were unlikely to have contributed significantly to the arrest.