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Immunotoxicity of Organotin Compounds. A Cell Biological Approach to Dialkyltin Induced Thymus Atrophy

  • Chapter
Immunotoxicology

Part of the book series: Developments in Hematology and Immunology ((DIHI,volume 16))

Abstract

In the last decade immunotoxicity has developed into a new area of drug and chemical toxicity as result of a growing number of compounds that are known to alter immunological responsiveness,either by an immunosuppression or an immunostimulation. The most conspicuous need is for much more information about the underlying molecular mechanisms. Only then will it be possible to explain why in some cases components of the immune system are so extremely sensitive. From reported data it is apparent that various compounds i.e. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,7,8-tetra chlorodi benzofuran (TCDF), polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), diethylstilbestrol (DES) and some di- and tri-alkyl substituted organotins act more or less preferentially on the thymus and therefore probably on thymus dependent functions (1–4). Although these compounds all produce thymic injury, they probably act at several different levels. To get more insight in the diand trialkyltin induced immune suppression studies our group has focussed on their ability to produce selective thymus atrophy. After a short overview of organotin applications, toxicity and immunosuppressive effects, the mechanisms that might be involved in the dialkyltin induced thymolytic effects are discussed in more detail.

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References

  1. Faith, R.E., M.I. Luster and J.G. Vos, 1980. Effects on immunocompetence by chemicals of environmental concern. In; Reviews in biochemical Toxicology (Eds. Hodgson, E., J.R. Bend and R.M. Philpot), Elsevier/North Holland, New York, Vol 2 173–212.

    Google Scholar 

  2. Vos, J.G. 1977. Immune suppression as related to toxicology, CRC Crit.Rev. Toxicol., 5 67–101

    Article  PubMed  CAS  Google Scholar 

  3. Vos, J.G., R.E. Faith and M.I. Luster 1980. Immune Alterations, Elsevier Holland Biomedical Press, Elsevier/North Holland, New York, 241–266.

    Google Scholar 

  4. Dean, J.H., M.I. Luster and G.A. Boorman 1982. Immunotoxicology, In Immonopharmacology (Eds Sirois, P. and M.R. Pleszczynski) elsevier Biomedical Press, New York, 349 - 397.

    Google Scholar 

  5. Laniganf D. and E.L. Weinberg, 1976. The use of Estertin Stabilizers in PVC, In Organotin Compounds: New Chemistry and Applications. (Ed. Zuckermann, J.J.) American Chemical Society, Washington, B.C., 134–154.

    Chapter  Google Scholar 

  6. Ross, A., 1965. Industrial application of organotic compounds, Ann. N.Y. Acad. Sci., 107–123.

    Google Scholar 

  7. Luyten, J.G.A. In Applications and Biological Effects of Organotin Compounds (Ed. Sawyer, A.K.) Dekker, New York, 3 931–974

    Google Scholar 

  8. Environmental Health Criteria, 15 1980. Tin and Organotin Compounds: A preliminary review, WHO, Geneva.

    Google Scholar 

  9. Cardarelli, N.F. 1974. Slow release molluscicides and related materials. In Molluscicides in schistosomiasis control (Ed. Cheng, T.C.) Academic Press, New York 177–240.

    Google Scholar 

  10. Duncan, J. 1980. The toxicology of Molluscicides. the Organotins, Pharmac. Ther., 10 407–429.

    Article  CAS  Google Scholar 

  11. Midwest Research Institute 1977. Assessment of the need for the character of, and the impact resulting from limitations on selected organotins. Phase I Assessment of the need for limitations on organotins. Washington, B.C., U.S. Environmental Protection Agency, EPA, contract No 68-01-4313.

    Google Scholar 

  12. Occupational exposure to Organotin Compounds, 1976. U.S. Department of Health, Education, and Welfare. U.S. Government Printing Office, Washington, D.C.

    Google Scholar 

  13. Alajonanine, T., Derobert, L. and Thieffry, S., 1958, Etude clinique d’ensemble de 210 cas d’intoxication par les sels organiques d’etain, Rev. Neurol., 98, 85–96.

    Google Scholar 

  14. Barnes, J.M. & Stoner, H.B., 1959, The toxicology of tin compounds, Pharmac. Rev., 11, 211–231.

    CAS  Google Scholar 

  15. Piver, W.T., 1973, Organotin Compounds: Industrial applications and biological investigation. Environ. Health Perspect., 4, 61–80

    Article  PubMed  CAS  Google Scholar 

  16. Barnes, J.M. & Magee, P.N., 1958, The biliary and hepatic lesion produced experimentally by dibutyltin salts, J. Pathol. Bacterid., 75, 267–279.

    Article  CAS  Google Scholar 

  17. Barnes, J.M. & Stöner, H.B., 1958, toxic properties of some dialkyltin and trialkyltin salts, Br. J. ind. Med., 15, 15–22.

    PubMed  CAS  Google Scholar 

  18. Pennihks, A.H. & Scinen, W., 1982, Comparative toxicity of alkyltin and estertin stabilizers, Fd. Chem. Toxicol., 20, 909–916.

    Article  Google Scholar 

  19. Chang, L.W., Tiemeyer, T.M., Gegner, G.R. & McMIIIan, D.E., 1983, Neuropathology of trimethyltin intoxication. III. Changes in the brain stem neurons. Environ. Res., 30, 399–411.

    Article  PubMed  CAS  Google Scholar 

  20. Watenabe, I., 1980, Organotins, In: Experimental and Clinical Neurotoxicity (Eds Spencer, P.S. & Schaumberg, H.H.) WIIIiams & Wilkins, Baltimore, 545–557.

    Google Scholar 

  21. Stoner, H.B., 1966, Toxicity of triphenyltin, Br. J. ind. Med., 23, 222–229.

    PubMed  CAS  Google Scholar 

  22. Scinen, W. & WIIIems, M.I., 1976, Toxicity of organotin compounds. I. Atrophy of thymus and thymus-dependent lymphoid tissue in rats fed di-n-octyltin dichloride, toxicol. Appl. Pharmacol., 35, 63–75.

    Article  Google Scholar 

  23. Scinen, W., Vos, J.G., van Spanje, I., Snoek, M., Brands, R. & Hooykaas, H., 1977, Toxicity of organotin compounds. II. Comparative in vivo and in vitro studies with various organotin and organolead compounds in different animal with various organotin and organolead compounds in different animal species with special emphasis on lymphocytotoxicity, Toxicol. Appl. Pharmacol., 42, 197–212.

    Article  Google Scholar 

  24. Scinen, W. & Pennihks, A.H., 1979, Immune suppression as a consequence of a selective cytotoxic activity of certain organometalic compounds on thymus-dependent lymphocytes, Ann. N.Y. Acad. Sci., 320, 499–517.

    Google Scholar 

  25. Pennihks, A.H. & Scinen, W., Detoxification of the estertin stabilizer Bis-( -carbobutoxyethylOtin dichloride in rats by hydrolysis of the esterbond. Submitted.

    Google Scholar 

  26. Scinen, W., Vos, J.G., van Krieken, R., Pennihks, A.H., Brands, R. & Hooykaas, H., 1977, Toxicity of organotin compounds. III. Suppression of thymus-dependent immu-nity in rats fed by di-n-butyltin dichloride and di-n-octyltin dichloride, Toxicol. Appl. Pharmacol., 42, 213–224

    Article  Google Scholar 

  27. Scinen, W., Vos, J.>., Brands, R. & Hooykaas, H., 1979, Lymphocyto toxicity and immunosuppression by organotin compounds. Suppression of GVH activity, blast transformation and E-rosette formation by di-n-butyltin dichlo-ride and di-n-octyltin dichloride, Immunopharmacol., 1, 343–355

    Article  Google Scholar 

  28. Scinen, W., 1981, Immunotoxicity of alkyltin compounds. In Immunologic considerations in Toxicology (Ed. Sharma, R.P.) Boca Raton: CRC Press, 1, 103–119.

    Google Scholar 

  29. Funahashi, N., Iwasahi, I. & Ide, G.I., 1980, Effects of bis(tri-n-butyltin) oxide on endocrine and lymphoid tissues of male rates. Acta Pathol. Jpn., 30, 955–966.

    PubMed  CAS  Google Scholar 

  30. Krajnc, E.I., Wester, P.W., Loeber, J.G., van Leeuwen, F.X.R., Vos, J.G., Vaessen, H.A.M.G. & van der Heyden, C.A., 1984, Toxicity of Bis (tri-n-butyltin)oxide in the rat. I. Short-time effects on general parameters and on the endocrine and lymphoid systems. Toxicol. Rppl. Pharmacol., 75, 363–386.

    Article  CAS  Google Scholar 

  31. Vos., J.G., de Klerk, A., Krajnc, E.I., Kruizinga, W., van Ommen, B. & Rozing, J., 1984, Toxicity of Bis (tri-n-butyltin)oxide in the rat. II. Suppression of thymus-dependent immune responses and parameters of non specific resistance after short-time exposure. Toxicol. Rppl. Pharmacol., 75, 387–408.

    Article  CAS  Google Scholar 

  32. Verschuuren, E.G., Ruitenberg, E.J., Peetoom, F., Helleman, P.W. & van Esch, G.J., 1970, Influence of triphenyltin acetate on lymphatic tissue and immune response in guinea pigs, Toxicol. Rppl. Pharmacol., 16, 400.

    Article  CAS  Google Scholar 

  33. Vos, J.G., van Logten, M.J., Kreeftenberg, J.G. & Kruizinga, W., 1984, Effect of triphenyltin hydroxide on the immune system of the rat, Toxicology, 29, 325–336.

    Article  PubMed  CAS  Google Scholar 

  34. Dougherthy, T.F., Berliner, M.L., Schneebeli, G.L. & Berliner, D.L., 1964, Hormonal control of lymphatic structure and function, Ann. N.Y. Read. Sci., 113, 825–843.

    Article  Google Scholar 

  35. Claesson, M.G. & Röpke, C., 1969, Quantitative studies on Cortisol induced decay of lymphoid cells in the thymolymphatic sustem, Rcta Pathol. Microbiol. Scand., 76, 367–382.

    Google Scholar 

  36. Thompson, H.R. & Gale, G.R., 1971, Cis-dichlorodiamicne platinum. II. Hematopoietic effects in rats, Toxicol. Rppl. Pharmacol., 19, 602–609.

    Article  CAS  Google Scholar 

  37. Miller, K., Scott, M.P. & Foster, J.B., 1984, Thymic involution in rats given diets containing dioctyltin dicloride, Clini. Immunol. Immunopathol., 30, 62–70.

    Article  CAS  Google Scholar 

  38. Penninks, A.H., Kuper, F., Spit, B.J. & Scinen, W., On the mechanism of dialkyItin induced thymus involution. Submitted.

    Google Scholar 

  39. Penninks, A.H. & Scinen, W., 1983, Tiie lymphocyte as target of toxicity: a biochemical approach to dialkyltin induced immunosuppression, In Advances in Immunopharmaco-logy (Eds Hadden, J.E. et al ), Pergamon Press, Oxford-New York, 2, 41–60.

    Google Scholar 

  40. Ernstroem, U., 1970, Hormonal influences on thymic release of lymphocytes into the blood, in Hormones and the immune response (Eds Wolstenholme, G.E.W. & Knight, J. ), ChurchIII J. & A. Publishers, 53.

    Google Scholar 

  41. Greaves, M.F., Owen J.J.T. & Raff, M.C., 1973, In: T and B lymphocytes, Excerpta Medica, Amsterdam, 13.

    Google Scholar 

  42. Mosier, D. & Cohen, P.L., 1975, Ontogeny of mouse T-lymphocyte function, Fed. Proc. Fed, Am. Soc. Exp. Biol., 34, 137–140.

    CAS  Google Scholar 

  43. Pierpaoli, W. & Sorkin, E., 1968, I. Effects of hetero-logues anti-growth hormone (ASTH) antiserum on thymus and peripheral lymphatic tissue in mice. Induction of wasting syndrome. J. Immunol., 101, 1036–1047.

    PubMed  CAS  Google Scholar 

  44. Pierpaoli, W., Baroni, C., Fabris, N. & Sorkin, E., 1969, Hormones and immunological capacity. II. Recon-stitution of anti-body production in hormonally deficient mice by somatotropic hormone, thyrotropic hormone and thyroxine, Immunol., 16, 217–229.

    CAS  Google Scholar 

  45. Haelst, U. van, 1967, Light and electronmicroscopic study of normal and pathological thymus of Ithe rat. II. The acute thymic involution, Zeitschr. fuer Zellforsch., 80, 153–182.

    Article  Google Scholar 

  46. Claesson, M.G., Jorgenson, O. & Olsson, L., 1972, Comparative light and electron microscopical studies of decaying thymic lymphoid cells, Acta pathol. Microbiol. Scand., 80, 821–826.

    CAS  Google Scholar 

  47. Metcalf, D. & Brumby, M., 1966, the role of the thymus in the ontogeny of the immune system, J. Cell. Physiol., 76, 1, 149–168.

    Article  Google Scholar 

  48. Weismann, I.L., 1976, Thymus cell migration, J. Exp. Med., 126, 291–294.

    Article  Google Scholar 

  49. Aldridge, W.N. & Cremer, J.E., 1955, The biochemistry of organotin compounds. Diethyltin dichloride and triethyl-tin sulphate, Biochem. J., 61, 406–418.

    PubMed  CAS  Google Scholar 

  50. Aldridge, W.N., 1976, The influence of organotin compounds on mitochondrial functions. In Organotin Compounds: New chemistry and application. (Ed. Zuchkermann, J.J._American Chemical Society, Washington, D.C., 186–196.

    Chapter  Google Scholar 

  51. Cain, K., Hyams, R.L. & Griffiths, D.E., 1977, Studies on the energy-linked reactions: Inhibition of oxidative phosphorylation and energy-linked reactions by dibutyltin dichloride, Feb Lett., 82, 23–28.

    Article  CAS  Google Scholar 

  52. Penniriks, A.H. & Scinen, W., 1980, Toxicity of organotin compounds. IV. Impairment of energy metabolism of rat thymocytes by various dialkyltin compounds, Toxicol. Appl. Pharmacol., 56, 221–231.

    Article  Google Scholar 

  53. Penninks, A.H., Verschuren, P.M. & Scinen, W., 1983, Di-n-butyltin dichloride uncouples oxidative phosphorylation in rat liver mitochondria, Toxicol. Appl. Pharmacol., 70, 115–120.

    Article  PubMed  CAS  Google Scholar 

  54. Griffiths, D.E., 1976, Studies on energy-linked reactions. Net synthesis of adenosine triphosphate by isolated adenosine triphosphate synthese preparations: A role for lipoic acid and unsaturated fatty acids, Biochem. J., 160, 809–812.

    PubMed  CAS  Google Scholar 

  55. Toninello, A. & Siliprandi, N., 1982, Restoration of membrane potential in mitochondria deenergized with carbonyl cyanide p-trifluoromethoxyphenylhydrazone ( FCCP ), Biochem. Biophys. Acta, 682, 289–292.

    Article  PubMed  CAS  Google Scholar 

  56. Kaback, H.R., Reeves, J.P., Short, S.A. & Lombard!, F.J., 1974, Mechanisms of active transport in isolated bacterial membrane vesicles. XVIII. The mechanism of action of Carbonylcyanide-m-Chlorophenylhydrazone, Arch. Biochem. Biophys., 160, 215–222.

    Article  PubMed  CAS  Google Scholar 

  57. Wiebkin, P., Prough, R.A. & Bridges, J.W., 1982, The metabolism and toxicity of some organotin compounds in isolatedrat hepatocytes, Toxicol. Appl. Pharmacol., 62, 409–42.

    Article  PubMed  CAS  Google Scholar 

  58. Kook, A.I. & Trainin, N., 1974, Hormone-like activity of a thymus humoral factor on the induction of immune competence in lymphoid cells, J. Exp. Med., 139, 193.

    Article  PubMed  CAS  Google Scholar 

  59. Goffey, R.G., Hadden, E.M. & Hadden, J.W., 1977, Evidence for cyclic GMP and Calcium mediation of lymphocyte activation by mitogens, J. Immunol., 119, 1387–1394.

    Google Scholar 

  60. Singh, U. & Owen, J.J.T., 1975, Studies on the effect of various agents in the maturation of thymus stem cells, Eur. J. Immunol., 5, 286–288.

    Article  PubMed  CAS  Google Scholar 

  61. Singh, U. & Owen, J.J.T., 1976, Studies on the maturation of thymus stem cells. The effect of catecholamines, histamine and peptide hormones on the expression of T cell alloantigens, Eur. J. Immunol., 6, 59–62.

    Article  PubMed  CAS  Google Scholar 

  62. Penninks, A.H. & Scinen, W., 1983, Immunotoxicity of organotin compounds. In Immunotoxicity (Eds Gibson, G.G., Hubbard, R. & Parke, D.V.) Academic Pres, London, 426–436.

    Google Scholar 

  63. Stoner, H.B., Barnes, J.M. & Duff, J.I., 1955, Studies on lthe toxicity of alkyltin compounds, Br. J. Pharmacol., 10, 16–25.

    CAS  Google Scholar 

  64. Rothstein, A., 1970, Sulfhydrylgroups in membrane structure and function. In Current tropics in Membranes and Transport. Academic Press, Nez-York-London, 1, 135–176.

    Google Scholar 

  65. Chaplin, D.D. & Wedner, H.J., 1978, Inhibition of lectin-induced lymphocyte activation by diamide and other sulfhydril reagents. Cell. Immunol., 36, 303–311.

    Article  PubMed  CAS  Google Scholar 

  66. Noelle, R.J. & Lawrence, D.A., 1981, Modulation of T-cell function. II. Chemical basis for the involvement of cell surface thiol-reactive sites of T-cell proliferation. Cell. Immunol., 60, 453–469.

    Article  PubMed  CAS  Google Scholar 

  67. Pfeifer, R.W. & Irons, R.D., 1981, Inhibition of lectin stimulated lymphocyte agglutination and mitogenesis by hydroquinone: reactivity with intracellular sulhydril groups, Exp. Mol. Pathol., 35, 189–198.

    Article  PubMed  CAS  Google Scholar 

  68. Pfeifer, R.W. & Irons, R.D., 1983, Alteration of lymphocyte function by quinones through a sulfhydryl dependent disruption of microtubule assembly, Int. J. Immunopharmacol., 5, 463–470.

    Article  PubMed  CAS  Google Scholar 

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  1. Working Group Pathology-Toxicology, Pathology-Toxicology Department, Faculty of Veterinary Sciences, State University of Utrecht, The Netherlands

    A. H. Penninks & W. Seinen

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Editors and Affiliations

  1. Commission of the European Communities, Luxembourg

    A. Berlin (Health and Safety Directorate) (Health and Safety Directorate)

  2. Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina, USA

    J. Dean

  3. International Programme on Chemical Safety, World Health Organization, Geneva, Switzerland

    M. H. Draper  & E. M. B. Smith  & 

  4. Institute of Pharmacological Research “Mario Negri”, Milan, Italy

    F. Spreafico

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© 1987 ECSC, EEC, EAEC, Brussels-Luxembourg and WHO, Geneva

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Penninks, A.H., Seinen, W. (1987). Immunotoxicity of Organotin Compounds. A Cell Biological Approach to Dialkyltin Induced Thymus Atrophy. In: Berlin, A., Dean, J., Draper, M.H., Smith, E.M.B., Spreafico, F. (eds) Immunotoxicology. Developments in Hematology and Immunology, vol 16. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4307-0_19

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  • DOI: https://doi.org/10.1007/978-94-009-4307-0_19

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-8414-7

  • Online ISBN: 978-94-009-4307-0

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