Analyze Diet
In vitro1984; 20(3 Pt 1); 198-204; doi: 10.1007/BF02618188

Spermidine cytotoxicity in vitro: effect of serum and oxygen tension.

Abstract: Plasma amine oxidase activities (benzylamine oxidase and spermine oxidase) were determined in the sera of a number of species of various ages. Benzylamine oxidase (BZO) activity, measured spectrophotometrically, was present in bovine, equine, and ovine species examined. Generally its activity in serum increased with the age of the animal. Spermine oxidase activity (SPO) was estimated by a bioassay of in vitro toxicity and did not necessarily correlate with BZO. Cytotoxicity in the presence of spermidine was found only in the sera of the ruminant species examined. Serum activity tended to rise with animal age; however, great variability was found in perinatal bovine sera. The 50% lethal dose (LD50) of spermidine in the presence of 5% serum and 4 X 10(4) NS1 cells/ml was in the micromolar range. Aminoguanidine, a known inhibitor of SPO, could prevent the cytotoxic effects of exogenously added spermidine in vitro. In contrast, raising the ambient oxygen tension in the incubation environment to 95% lowered the LD50 dose of spermidine required for cytotoxicity. The results suggest that a cell line of hematogenous origin is susceptible to the cytotoxic effects of the products of oxidative deamination of spermidine by SPO, an enzyme present in perinatal bovine sera, and that these cytotoxic effects are potentiated in the presence of an oxygen-enriched environment in vitro.
Publication Date: 1984-03-01 PubMed ID: 6715006DOI: 10.1007/BF02618188Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Comparative Study
  • Journal Article
  • Research Support
  • U.S. Gov't
  • P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on the in vitro cytotoxicity of Spermidine and how it is affected by serum and oxygen tension. The study unearths the key role of plasma amine oxidase activities, and their increase with age, in the resultant cytotoxic effects, while also highlighting that higher oxygen levels can intensify these effects.

Discussion on Plasma Amine Oxidase Activities

  • The researchers measured the activities of plasma amine oxidase activities, specifically benzylamine oxidase (BZO) and spermine oxidase (SPO), in the sera of various species at different ages.
  • The BZO activity was observed in bovine, horse, and sheep, with its activity generally increasing as the animal aged. This activity was measured spectrophotometrically.
  • SPO activity, however, did not necessarily correspond with BZO activity.

Spermidine Cytotoxicity

  • The cytotoxic effects of spermidine were uniquely observed in the sera of ruminants. This implies that the cytotoxicity of spermidine varied among different species.
  • Serum activity tended to rise as the animal aged, much like BZO; however, there were significant deviations in perinatal bovine sera.
  • The lethal dose of spermidine, under the conditions of 5% serum and 4 X 10(4) NS1 cells/ml, was within the micromolar range. This shows that the cytotoxic effects of spermidine can be profound at a relatively low concentration.

Impact of Aminoguanidine and Oxygen Tension

  • The cytotoxic effects of spermidine could be thwarted by aminoguanidine, an inhibitor of SPO. This suggests a relationship between SPO and spermidine cytotoxicity.
  • Increasing the ambient oxygen tension to 95% significantly reduced the required lethal dose of spermidine. This finding indicated that higher oxygen levels could potentiate the cytotoxic effects of spermidine.

Summary

  • The study concludes that a specific cell line of hematogenous origin can suffer cytotoxic effects from oxidative deamination products of spermidine, an occurrence mediated by SPO.
  • The enzyme SPO, found in perinatal bovine sera, was crucial in this process. The presence of an oxygen-rich environment in vitro significantly enhanced these cytotoxic effects.

Cite This Article

APA
Hegre OD, Marshall S, Hickey GE. (1984). Spermidine cytotoxicity in vitro: effect of serum and oxygen tension. In Vitro, 20(3 Pt 1), 198-204. https://doi.org/10.1007/BF02618188

Publication

ISSN: 0073-5655
NlmUniqueID: 0063733
Country: United States
Language: English
Volume: 20
Issue: 3 Pt 1
Pages: 198-204

Researcher Affiliations

Hegre, O D
    Marshall, S
      Hickey, G E

        MeSH Terms

        • Aging
        • Animals
        • Benzylamine Oxidase / blood
        • Cattle / blood
        • Cell Line
        • Cell Survival / drug effects
        • Chickens / blood
        • Guanidines / pharmacology
        • Horses / blood
        • Kinetics
        • Lethal Dose 50
        • Mice
        • Monoamine Oxidase / blood
        • Oxidoreductases Acting on CH-NH Group Donors / blood
        • Oxygen / pharmacology
        • Plasmacytoma
        • Sheep / blood
        • Spermidine / toxicity

        Grant Funding

        • AM 19899 / NIADDK NIH HHS
        • AM 32237 / NIADDK NIH HHS
        • HD 00412 / NICHD NIH HHS

        References

        This article includes 26 references
        1. Gaugas JM, Curzen P. Polyamine interaction with pregnancy serum in suppression of lymphocyte transformation.. Lancet 1978 Jan 7;1(8054):18-20.
          pubmed: 74498doi: 10.1016/s0140-6736(78)90363-xgoogle scholar: lookup
        2. HIRSCH JG. Spermine oxidase: an amine oxidase with specificity for spermine and spermidine.. J Exp Med 1953 Mar;97(3):345-55.
          pubmed: 13052805doi: 10.1084/jem.97.3.345google scholar: lookup
        3. Gaugas JM, Dewey DL. Oxygen-dependent free radicals in spermine oxidation cytostatis and chemiluminescence and the role of superoxide dismutase.. Br J Cancer 1980 Jun;41(6):946-55.
          pubmed: 7426319doi: 10.1038/bjc.1980.173google scholar: lookup
        4. Yasunobu KT, Ishizaki H, Minamiura N. The molecular mechanistic and immunological properties of amine oxidases.. Mol Cell Biochem 1976 Oct 30;13(1):3-29.
          pubmed: 187928doi: 10.1007/BF01732392google scholar: lookup
        5. Pegg AE, Seely JE, Pösö H, della Ragione F, Zagon IA. Polyamine biosynthesis and interconversion in rodent tissues.. Fed Proc 1982 Dec;41(14):3065-72.
          pubmed: 7141002
        6. Morgan DM, Illei G. Radiochemical estimation of serum polyamine oxidase activity in human pregnancy.. Med Lab Sci 1981 Jan;38(1):49-56.
          pubmed: 7266276
        7. TABOR CW, TABOR H, BACHRACH U. IDENTIFICATION OF THE AMINOALDEHYDES PRODUCED BY THE OXIDATION OF SPERMINE AND SPERMIDINE WITH PURIFIED PLASMA AMINE OXIDASE.. J Biol Chem 1964 Jul;239:2194-203.
          pubmed: 14209948
        8. JAENNE J, RAINA A, SIIMES M. SPERMIDINE AND SPERMINE IN RAT TISSUES AT DIFFERENT AGES.. Acta Physiol Scand 1964 Dec;62:352-8.
        9. BLASCHKO H, HAWES R. Observations on spermine oxidase of mammalian plasma.. J Physiol 1959 Jan 28;145(1):124-31.
        10. Webber MM, Chaproniere-Rickenberg D. Spermine oxidation products are selectively toxic to fibroblasts in cultures of normal human prostatic epithelium.. Cell Biol Int Rep 1980 Feb;4(2):185-93.
          pubmed: 7388968doi: 10.1016/0309-1651(80)90073-9google scholar: lookup
        11. MCEWEN CM Jr, COHEN JD. AN AMINE OXIDASE IN NORMAL HUMAN SERUM.. J Lab Clin Med 1963 Nov;62:766-76.
          pubmed: 14078013
        12. Jensen PK, Therkelsen AJ. Selective inhibition of fibroblasts by spermine in primary cultures of normal human skin epithelial cells.. In Vitro 1982 Oct;18(10):867-71.
          pubmed: 7173947doi: 10.1007/BF02796328google scholar: lookup
        13. Morgan DM, Illei G. Polyamine-polyamine oxidase interaction: part of maternal protective mechanism against fetal rejection.. Br Med J 1980 May 31;280(6227):1295-7.
          pubmed: 7388515doi: 10.1136/bmj.280.6227.1295google scholar: lookup
        14. Gahl WA, Pitot HC. Reversal by aminoguanidine of the inhibition of proliferation of human fibroblasts by spermidine and spermine.. Chem Biol Interact 1978 Jul;22(1):91-8.
          pubmed: 99252doi: 10.1016/0009-2797(78)90152-7google scholar: lookup
        15. Russell DH, Medina VJ, Snyder SH. The dynamics of synthesis and degradation of polyamines in normal and regenerating rat liver and brain.. J Biol Chem 1970 Dec 25;245(24):6732-8.
          pubmed: 5482776
        16. Russell D, Snyder SH. Amine synthesis in rapidly growing tissues: ornithine decarboxylase activity in regenerating rat liver, chick embryo, and various tumors.. Proc Natl Acad Sci U S A 1968 Aug;60(4):1420-7.
          pubmed: 4299947doi: 10.1073/pnas.60.4.1420google scholar: lookup
        17. Lafferty KJ, Cooley MA, Woolnough J, Walker KZ. Thyroid allograft immunogenicity is reduced after a period in organ culture.. Science 1975 Apr 18;188(4185):259-61.
          pubmed: 1118726doi: 10.1126/science.1118726google scholar: lookup
        18. Katsuta H, Takaoka T, Nose K, Nagai Y. Effects of polyamines on the proliferation of mammalian cells in tissue culture.. Jpn J Exp Med 1975 Oct;45(5):345-54.
          pubmed: 177793
        19. Allen JC, Smith CJ, Hussain JI, Thomas JM, Gaugas JM. Inhibition of lymphocyte proliferation by polyamines requires ruminant-plasma polyamine oxidase.. Eur J Biochem 1979 Dec;102(1):153-8.
        20. Bowen KM, Andrus L, Lafferty KJ. Successful allotransplantation of mouse pancreatic islets to nonimmunosuppressed recipients.. Diabetes 1980;29 Suppl 1:98-104.
          pubmed: 6766418doi: 10.2337/diab.29.1.s98google scholar: lookup
        21. Williams-Ashman HG, Canellakis ZN. Polyamines in mammalian biology and medicine.. Perspect Biol Med 1979 Spring;22(3):421-53.
          pubmed: 471697doi: 10.1353/pbm.1979.0013google scholar: lookup
        22. Serie JR, Hickey GE, Schmitt RV, Hegre OD. Prolongation of culture-isolated neonatal islet xenografts without immunosuppression.. Transplantation 1983 Jul;36(1):6-11.
        23. Byrd WJ, Jacobs DM, Amoss MS. Synthetic polyamines added to cultures containing bovine sera reversibly inhibit in vitro parameters of immunity.. Nature 1977 Jun 16;267(5612):621-3.
          pubmed: 141619doi: 10.1038/267621a0google scholar: lookup
        24. Gaugas JM, Dewey DL. Evidence for serum binding of oxidized spermine and its potent G1-phase inhibition of cell proliferation.. Br J Cancer 1979 May;39(5):548-57.
          pubmed: 486311doi: 10.1038/bjc.1979.100google scholar: lookup
        25. Lacy PE, Finke EH, Janney CG, Davie JM. Prolongation of islet xenograft survival by in vitro culture of rat megaislets in 95% O2.. Transplantation 1982 Jun;33(6):588-92.
        26. Horibata K, Harris AW. Mouse myelomas and lymphomas in culture.. Exp Cell Res 1970 Apr;60(1):61-77.
          pubmed: 5439579doi: 10.1016/0014-4827(70)90489-1google scholar: lookup

        Citations

        This article has been cited 2 times.
        1. Nilson R, Lübbers O, Weiß L, Singh K, Scharffetter-Kochanek K, Rojewski M, Schrezenmeier H, Zeplin PH, Funk W, Krutzke L, Kochanek S, Kritzinger A. Transduction Enhancers Enable Efficient Human Adenovirus Type 5-Mediated Gene Transfer into Human Multipotent Mesenchymal Stromal Cells.. Viruses 2021 Jun 12;13(6).
          doi: 10.3390/v13061136pubmed: 34204818google scholar: lookup
        2. Parchment RE, Natarajan K. A free-radical hypothesis for the instability and evolution of genotype and phenotype in vitro.. Cytotechnology 1992;10(2):93-124.
          doi: 10.1007/BF00570888pubmed: 1369214google scholar: lookup