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Lack of a relationship between immune function and chemically induced hepatocarcinogenesis in B6C3F1 mice

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Summary

The relationship between immune function and chemically induced hepatocarcinogenesis was studied employing an in vivo murine model. Neonatal B6C3F1 mice were given a single carcinogenic dose of diethylnitrosamine (DEN) and the time-response kinetics for the early (foci of alteration) and late (adenomas/carcinomas) phases of hepatocellular carcinogenesis were compared to changes in hematopoiesis and immune functions associated with immune surveillance and natural resistance. Increases in hematopoiesis occurred just prior to or concurrent with the appearance of hepatocellular carcinomas, while increased macrophage and natural killer cell cytotoxicity and suppression of cell-mediated immunity occurred following tumor appearance and progressed with increasing tumor burden. Neither immunological nor hematopoietic changes were associated with early phases of hepatocarcinogenesis, as monitored by the appearance of altered hepatocellular foci. Although changes in hematopoiesis may represent an early indicator for hepatocarcinogenesis in the mouse tumor model, the data suggest that altered immune surveillance and natural resistance are not factors in the development of chemically induced hepatocellular tumors, and the changes in immune function are probably secondary to tumor development.

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References

  1. 1.

    Albright JW, Albright JF (1983) Age associated impairment of murine NK cell activity. Proc Natl Acad Sci USA 80:6371

  2. 2.

    Balducci L, Hardy C (1983) High proliferation of granulocyte-macrophage progenitors in tumor-bearing mice. Exp Hematol 43:4643

  3. 3.

    Blasecki JW (1981) Induction and inhibition of the immune response to tumors induced by simian virus 40 (SV40). In: Waters H (ed) The handbook of cancer immunology, volume 8, tumor antigens: structure and function. STPM Garland Press, New York, p 418

  4. 4.

    Boorman GA, Luster MI, Dean JH, Campbell ML (1982) Assessment of myelotoxicity caused by environmental chemicals. Environ Health Perspect 43:129

  5. 5.

    Brodt P, Lala PK (1983) Changes in the host lymphocyte subsets during chemical carcinogenesis. Cancer Res 143:4315

  6. 6.

    Forbes JT, Greco FA, Oldham RK (1980) Natural cell-mediated cytotoxicity in human tumor patients. In: Natural cell-mediated immunity against tumors. Academic Press, New York, p 1031

  7. 7.

    Garnis S, Lala PK (1978) Surface markers of small lymphocytes appearing in the mouse Ehrlich ascites tumor, host spleen and blood. Immunology 34:487

  8. 8.

    Hanna N, Burton RC (1981) Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastases in vivo. J Immunol 127:1754

  9. 9.

    Herberman RB (1985) Immunological mechanisms of host resistance to tumors. In: Immunotoxicology and immunopharmacology. Raven Press, New York, p 511

  10. 10.

    Herberman RB, Holden HT, Djeu JY, Jerrells TR, Varesio L, Tagliabue A, White SL, Oehler JR, Dean JH (1980) Macrophages as regulators of immune responses against tumors. In: Macrophages and lymphocytes. Plenum Pub Corp, New York, p 361

  11. 11.

    Ideka K, Motoyoshi K, Ishizaka Y, Hatake K, Kajigaya S, Saito M, Miura Y (1985) Human colony-stimulating activity-producing tumor: Production of very low mouse-active colony-stimulating activity and induction of marked granulocytosis in mice. Cancer Res 45:4144

  12. 12.

    Kay MMB, Makinodan T (1976) Immunobiology of aging: Evaluation of current status. Clin Immunol Immunopathol 6:394

  13. 13.

    Kovacs CJ, Emma DA, Evans MJ, Johnke RM, Scarantino CW (1985) Haemopoietic modulation in tumour-bearing animals: Enhanced progenitor cell production in femoral marrow. Cell Tissue Kinet 18:235

  14. 14.

    Kruisbect AM, Zijlstra J, Zurcher C (1978) Tumor-induced changes in T cell mitogen responses in rats: Suppression of spleen and blood lymphocyte responses and enhancement of thymocyte responses. Eur J Immunol 8:200

  15. 15.

    Lala PK, Santes V, Libenson H, Parhar RS (1985) Changes in the host natural killer cell population in mice during tumor development. Cell Immunol 93:250

  16. 16.

    Leu RW, Norton TR, Herriott MJ, Ringer DP, Kearns RJ (1985) Suppression of natural killer and lymphocyte functions associated with carcinogen-induced premalignant hyperplastic nodules in rat liver. Cancer Res 45:3282

  17. 17.

    Luster MI, Tucker AN, Hayes HT, Pung OJ, Burka T, McMillan R, Eling T (1985) Immunosuppressive effects of benzidine in mice: Evidence of alterations in arachidonic acid metabolism. J Immunol 135:2754

  18. 18.

    Luster MI, Germolec DR, Burleson GR, Jameson CW, Ackermann MF, Lamm KR, Hayes HT (1987) Selective immunosuppression in mice of natural killer cell activity by ochratoxin A. Cancer Res 47:2259

  19. 19.

    Maronpot RR, Haseman JK, Boorman GA, Eustis SE, Rao GN, Huff JE (1987) Liver lesions in B6C3F1 mice: The National Toxicology Program experience and position. Arch Toxicol Suppl 10:10

  20. 20.

    Murray MJ, Lauer LD, Luster MI, Luebke RW, Adams DO, Dean JH (1985) Correlation of murine susceptibility to tumor, parasite and bacterial challenge with altered cell-mediated immunity following systemic exposure to the tumor promoter phorbol myristate acetate. Int J Immunopharmacol 7:491

  21. 21.

    Otter WD (1986) Immune surveillance and natural resistance: An evaluation. Cancer Immunol Immunother 21:85

  22. 22.

    Purtilo DT, Linder J (1983) Oncological consequences of impaired immune surveillance against ubiquitous viruses. J Clin Immunol 3:197

  23. 23.

    Reynolds CW, Herberman RB (1981) In vitro augmentation of rat natural killer (NK) cell activity. J Immunol 126:1581

  24. 24.

    Santer V, Mastromarino JH, Lala PK (1980) Characterization of lymphocyte subsets in spontaneous mouse mammary tumors and host lymphoid organs. Int J Cancer 25:159

  25. 25.

    Stutman O (1979) Chemical carcinogenesis in nude mice from homozygous matings and heterozygous matings and effect of age and carcinogen dose. J Natl Cancer Inst 62:353

  26. 26.

    Trutin-Ostovic C, Golubic M, Matovic M, Marusic M (1986) Incidence and growth of methylcholanthrene-induced tumors in mice with altered immunological status. Cancer Immunol Immunother 23:130

  27. 27.

    Varesio L, Holden HT, Taramelli HT (1980) Mechanism of lymphocyte activation. II. Requirements for macromolecular synthesis in the production of lymphokines. J Immunol 125:2810

  28. 28.

    Vesselinovitch SD, Mihailovich N (1983) Kinetics of diethylnitrosamine hepatocarcinogenesis in the infant mouse. Cancer Res 43:4253

  29. 29.

    Wanebo HJ, Pinsky CM, Beattie EJ, Oettgen HF (1979) Immunocompetence testing in patients with one of the common operable cancers — A review. In: Flad HD, Herfarth C, Betzler M (eds) Immunodiagnosis and immunotherapy of malignant tumors: relevance to surgery. Springer-Verlag, New York, p 329

  30. 30.

    Young MR, Newby M, Wepsic HT (1987) Hematopoiesis and suppressor bone marrow cells in mice bearing large metastatic Lewis lung carcinoma tumors. Cancer Res 47:100

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Correspondence to Dori R. Germolec.

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Germolec, D.R., Maronpot, R.R., Ackermann, M.F. et al. Lack of a relationship between immune function and chemically induced hepatocarcinogenesis in B6C3F1 mice. Cancer Immunol Immunother 27, 121–127 (1988). https://doi.org/10.1007/BF00200015

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Keywords

  • Natural Killer
  • Hepatocellular Carcinoma
  • Natural Killer Cell
  • Immune Function
  • Cell Cytotoxicity