Biogenic polyamine formed from spermidine, q.v., and occurring in almost all tissues. Essential for both normal and neoplastic tissue growth. First observed in human semen and described as the cryst phosphate salt by A. von Leeuwenhoek, Philos. Trans. R. Soc. London 12, 1040 (1678). For a description of the history, occurrence, formation, and early prepns of spermine, see Beilstein vol. IV, Suppl. 1, 704; M. Guggenheim, Die biogenen Amine (S. Karger, Basel, 4th ed., 1951) 619 pp; H. Tabor et al., Annu. Rev. Biochem. 30, 579-604 (1961). Prepn of spermine and its tetrahydrochloride: Israel et al., J. Med. Chem. 7, 710 (1964). Role in cell growth processes: C. W. Tabor, H. Tabor, Annu. Rev. Biochem. 45, 285 (1976); J. Janne et al., Biochim. Biophys. Acta 473, 241 (1978). Modulation of calcium-dependent immune processes: T. C. Theoharides, Life Sci. 27, 703 (1980). Biosynthesis in fungi: L. Stevens, Med. Biol. 59, 308 (1981). HPLC study: C. E. Prussak, D. H. Russell, J. Chromatogr. 229, 47 (1982). Use as a biochemical marker for malignant tumors: Y. Horn et al., Cancer Res. 42, 3248 (1982). Metabolic study: A. E. Pegg et al., Biochemistry 21, 5082 (1982). Review of role in cell proliferation and differentiation: O. Heby, Differentiation 19, 1-20 (1981). Book: Polyamines in Biology and Medicine D. R. Morris, L. J. Marton, Eds. (Dekker, New York, 1981) 512 pp.