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Effect of dietary polyunsaturated fat and 7,12-dimethylbenz(a)-anthracene on rat splenic natural killer cells and prostaglandin E synthesis

Summary

Dietary polyunsaturated fat has been shown to stimulate mammary tumorigenesis induced in rats by 7,12-dimethylbenz(a)anthracene (DMBA). Studies were undertaken to investigate the effect of polyunsaturated fat and DMBA on splenic natural killer (NK) activity and prostaglandin E (PGE) synthesis. In a first experiment, splenic NK activity at 33, 55, 75, and 110 days of age was measured in Sprague-Dawley rats fed 0.5% low fat (LF), 5% normal fat (NF), or 20% high fat (HF) corn oil diets from 23 days of age. At 55 days of age, half of the rats from the 75 and 110 day age groups were given 5 mg DMBA. Ten days after the initiation of the diets splenic NK activity against YAC-1 lymphoma was decreased from 50% cytotoxicity in rats fed NF diet to 21% cytotoxicity in rats fed HF diet, but was not affected by LF feeding. No difference in NK activity was observed among the groups at the later time periods. DMBA had no effect on NK activity at 20 or 55 days after its administration. In a second experiment, where DMBA (15 mg/rat) was given to half of the rats at 50 days of age and NF or HF diets were started 3 days later, NK activity was 35% in rats fed NF diet and 21% in rats fed HF diet, 5 days after the diets were started. No difference in NK activity in rats fed either diet was observed at later time periods. DMBA decreased both NK activity and spleen cellularity transiently. In both experiments, PGE synthesis by spleen cells cultured for 18 h was not affected by dietary fat intake, but was slightly increased 3 days after DMBA administration. Results from these experiments suggest that the stimulation of DMBA-induced mammary tumorigenesis by polyunsaturated fat and by DMBA itself may possibly be mediated by a transient decrease in splenic NK cell activity.

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References

  1. 1.

    Barlozzari T, Reynolds CW, Herberman RB (1983) In vivo role of natural killer cells: involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GM1-treated rats. J Immunol 131:1024–1027

  2. 2.

    Brunda MJ, Herberman RB, Holden H (1980) Inhibition of murine natural killer cell activity by prostaglandin. J Immunol 124:2682–2687

  3. 3.

    Carter CA, Milholland RJ, Shea W, Ip MM (1983) Effect of the prostaglandin synthetase inhibitor indomethacin on 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat. Cancer Res 43:3559–3562

  4. 4.

    Droller M, Shneider MU, Perlmann P (1978) A possible role of prostaglandins in the inhibition of natural and antibody-dependent cell-mediated cytotoxicity against tumor cells. Cell Immunol 35:165–177

  5. 5.

    Ehrlich R, Efrati M, Ber-Eyal A, Wollberg M, Schilby G, Ran M, Witz IP (1980) Natural cellualr reactivities mediated by splenocytes from mice bearing three types of primary tumor. Int J Cancer 26:315–323

  6. 6.

    Goodwin JS, Ceuppens J (1983) Regulation of the immune response by prostaglandins. J Clin Immunol 3:295–315

  7. 7.

    Gorelik E, Herberman RB (1981) Inhibition of the activity of mouse natural killer cells by urethan. J Natl Cancer Inst 66:543–548

  8. 8.

    Haller O, Hansson M, Kiessling R, Wigzell H (1977) Role of non-conventinal natural killer cells in resistance against syngeneic tumor cells in vivo. Nature 270:609–611

  9. 9.

    Hanna N, Burton RC (1981) Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasis in vivo. J Immunol 127:1754–1758

  10. 10.

    Ip C, Sinha D (1981) Neoplastic growth of carcinogen-treated mammary transplants as influenced by fat intake of donor and host. Cancer Lett 11:277–283

  11. 11.

    Kalland T, Forsberg J-G (1983) 3-Methylcholanthrene: transient inhibition of the lytic step of mouse natural killer cells. J Natl Cancer Inst 71:385–390

  12. 12.

    Kennedy MS, Stobo JD, Goldyne ME (1980) In vitro synthesis of prostaglandins and related lipids by populations of human peripheral blood monocyttes. Prostaglandins 20:135–145

  13. 13.

    Leung KH, Koren HS (1982) Regulation of human natural killing II. Protective effect of interferon on NK cells from suppression by PGE2. J Immunol 129:1742–1747

  14. 14.

    Leung KH, Mihich E (1982) Effects of prostaglandins on the development of cell-mediated immunity in culture and on the cytolytic activity of in vivo-generated effector cells. Int J Immunopharmacol 4:205–217

  15. 15.

    Leung KH, Koren HS (1984) Regulation of human natural killing III. Mechanism for interferon induction of loss of susceptibility to suppression by cyclic AMP elevating agents. J Immunol 132:1445–1450

  16. 16.

    Leung KH, Ip MM (1984) Inhibition of rat natural killer (NK) activity and NK activation by inhibitors of lipoxygenase (LO) and protein synthesis (PS). Fed Proc 43:663

  17. 17.

    Leung KH, Ehrke MJ, Mihich E (1982) Modulation of the development of cell-mediated immunity: possible role of the products of the cyclo-oxygenase and the lipoxygenase pathways of arachidonic acid metabolism. Int J Immunopharmacol 4:195–204

  18. 18.

    Leung KH, Fischer DG, Koren HS (1983) Erythromyeloid tumor cells (K562) induce PGE synthesis in human peripheral blood monocytes. J Immunol 131:445–449

  19. 19.

    Plescia OJ, Grinwich K, Plesica AM (1976) Subversive activity of syngeneic tumor cells as an escape mechanism from immune surveillance and the role of prostaglandins. Ann NY Acad Sci 276:455–465

  20. 20.

    Welsch CW, Aylsworth CF (1983) Enhancement of murine mammary tumorigenesis by feeding high levels of dietary fat: A hormonal mechanism J Natl Cancer Inst 70:215–221

  21. 21.

    Kollmorgen GM, King MM, Kosanke SD, Do C (1983) Influence of dietary fat and indomethacin on the growth of transplantable mammary tumors in rats. Cancer Res 43:4714–19

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Author information

Correspondence to Kam H. Leung.

Additional information

This work was supported by grants CA-35641, CA-33240, CA-13038 and Core Grant CA-24538 from the National Cancer Institute

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Leung, K.H., Ip, M.M. Effect of dietary polyunsaturated fat and 7,12-dimethylbenz(a)-anthracene on rat splenic natural killer cells and prostaglandin E synthesis. Cancer Immunol Immunother 21, 161–163 (1986). https://doi.org/10.1007/BF00199865

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Keywords

  • Anthracene
  • DMBA
  • Natural Killer Cell Activity
  • Natural Killer Activity
  • Mammary Tumorigenesis