Enhancement of Pancreatic Carcinogenesis by Raw Soy Protein Isolate: Quantitative Rat Model and Nutritional Considerations

  • B. D. Roebuck
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 199)


Foods containing soybean products have been shown to modify the biochemical and physiological status of the pancreas of several species of experimental animals. Recently, these products have been implicated as a factor in the causation of pancreatic neoplasms. Extensive experimental studies into the possible mechanisms need to be undertaken. Experimental details of a rat/azaserine model for the study of pancreatic carcinogenesis are reviewed. Emphasis is given to the quantitative components of this model and the adaptation of this model to the two-stage (initiation-promotion) concept of carcinogenesis. Particular attention is devoted to considerations of the experimental diets. Application of these concepts to the study of the postinitiational effects of raw and heated soybean protein isolate with and without the addition of high levels of unsaturated fat were undertaken. The results indicate that raw soybean isolate enhanced the growth of azaserine-induced pancreatic foci; whereas, a high level of unsaturated fat had a minimal effect. The effects of the soybean isolate were abolished by heat treatments, but the effects of the unsaturated fat would not be expected to be abolished by similar treatment with heat.


Acinar Cell Soybean Product Pancreatic Carcinogenesis Pancreatic Hypertrophy Normal Acinar Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Adrian, T.E., Pasquali, C., Pescosta, F., Bacarese-Hamilton, A.J. and Bloom, S.R., 1982, Soya induced pancreatic hypertrophy and rise in circulating cholecystokinin, Gut, 23:A889.Google Scholar
  2. 2.
    Bieri, J., 1977, Report of the American Institute of Nutrition Ad Hoc Committee on standards of nutritional studies, J. Nutr., 107:1340–1348.Google Scholar
  3. 3.
    Bieri, J., 1980, Second report of the ad hoc committee on standards for nutritional studies, J. Nutr., 110:1726.Google Scholar
  4. 4.
    Birt, D.F., Salmasi, S. and Pour, P.M., 1981, Enhancement of experimental pancreatic cancer in Syrian golden hamsters by dietary fat, J. Natl. Cancer Inst., 67:1327–1332.Google Scholar
  5. 5.
    Boorman, G.A. and Eustis, S.L., 1984, Proliferative lesions of the exocrine pancreas in male F344/N rats, Environ. Health Prospect., 56:213–217.CrossRefGoogle Scholar
  6. 6.
    Booth, A.N., Robbins, D.J., Ribelin, W.E. and DeEds, F., 1960, Effects of raw soybean meal and amino acids on pancreatic hypertrophy in rats, Proc. Soc. Exp. Biol. Med., 104:68l–683.Google Scholar
  7. 7.
    Chernick, S.S., Lepkovsky, S. and Chaikoff, I.L., 1948, A dietary factor regulating the enzyme content of the pancreas: Changes indiced in size and proteolytic activity of the chick pancreas by the ingestion of raw soy-bean meal, Am. J. Physiol., 155:33–41.Google Scholar
  8. 8.
    Chiu, T., 1983, Spontaneous hypertrophic foci of pancreatic acinar cells in CD rats, Toxicol. Pathol., 11:115–119.CrossRefGoogle Scholar
  9. 9.
    Chiu, T., 1985, Hypertrophic foci of pancreatic acinar cells in rats, CRC Critical Rev. Toxicol., 14:133–157.CrossRefGoogle Scholar
  10. 10.
    Crass, R.A. and Morgan, R.G.H., 1981, Rapid changes in pancreatic DNA, RNA and protein in the rat during pancreatic enlargement and involution, Int. J. Vitam. Nutr. Res., 51:85–91.Google Scholar
  11. 11.
    Dijkhof, J., Poort, S.R. and Poort, C., 1977, Effect of feeding soybean flour containing diets on the protein synthetic pattern of the rat pancreas, J. Nutr., 107:1985–1995.Google Scholar
  12. 12.
    Farber, E., 1984, The multistep nature of cancer development, Cancer Res., 44:4217–4223.Google Scholar
  13. 13.
    Folsch, U.R., Winckler, K. and Wormsley, K.G., 1974, Effect of a soybean diet on enzyme content and ultrastructure of the rat exocrine pancreas, Digestion, 11:161–171.CrossRefGoogle Scholar
  14. 14.
    Fox, J.G., Thibert, P., Arnold, D.L., Krewski, D.R. and Grice, H.C., 1979, Toxicology studies. II. The laboratory animal, Fd. Cosmet. Toxicol., 17:661–675.CrossRefGoogle Scholar
  15. 15.
    Green, G.M. and Lyman, R.L., 1972, Feedback regulation of pancreatic enzyme secretion as a mechanism for trypsin inhibitor-induced hypersecretion in rats, Proc. Soc. Exp. Biol. Med., 140:6–12.Google Scholar
  16. 16.
    Levison, D.A., Morgan, R.G.H., Brimacombe, J.S., Hopwood, D., Coghill, G. and Wormsley, K.G., 1979, Carcinogenic effects of di(2-hydroxypropyl) nitrosamine (DHPH) in male Wistar rats: Promotion of pancreatic cancer by raw soya flour diet, Scand. J. Gastroent., 14:217–224.CrossRefGoogle Scholar
  17. 17.
    Longnecker, D.S., 1984, Lesions induced in rodent pancreas by azaserine and other pancreatic carcinogens, Environ. Health Prospect., 56:245–251.CrossRefGoogle Scholar
  18. 18.
    Longnecker, D.S., Curphey, T.J., Kuhlmann, E.T. and Roebuck, B.D., 1982, Inhibition of pancreatic carcinogenesis by retinoids in azaserine-treated rats, Cancer Res., 42:19–24.Google Scholar
  19. 19.
    Longnecker, D.S., Wiebkin, P., Shaeffer, B.K. and Roebuck, B.D., 1984, Experimental carcinogenesis in the pancreas, Int. Rev. Exp. Pathol., 26:177–229.Google Scholar
  20. 20.
    McGuinness, E.E., Hopwood, D. and Wormsley, K.G., 1982, Further studies on the effects of raw soya flour on rat pancreas, Scand. J. Gastroent., 17:273–277.CrossRefGoogle Scholar
  21. 21.
    McGuinness, E.E., Morgan, R.G.H., Levison, D.A., Frape, D.L., Hopwood, D. and Wormsley, K.G., 1980, The effects of long-term feeding of soya flour on the rat pancreas, Scand. J. Gastroent., 15:497–502.CrossRefGoogle Scholar
  22. 22.
    McGuinness, E.E., Morgan, R.G.H., Levison, D.A., Hopwood, D. and Wormsley, K.G., 1981, Interaction of azaserine and raw soya flour on the rat pancreas, Scand. J. Gastroent., 16:49–56.Google Scholar
  23. 23.
    McGuinness, E.E., Morgan, R.G.H. and Wormsley, K.G., 1984, Effects of soybean flour on the pancreas of rats, Environ. Health Prospect., 56: 205–212.CrossRefGoogle Scholar
  24. 24.
    Melmed, R.N., El-Aaser, A.A.A. and Holt, S.J., 1976, Hypertrophy and hyperplasia of the neonatal rat exocrine pancreas induced by orally administered soybean trypsin inhibitor, Biophys. Acta, 421:280–288.CrossRefGoogle Scholar
  25. 25.
    Morgan, R.G.H., Levinson, D.A., Hopwood, D., Saunders, J.H.B. and Wormsley, K.G., 1977, Potential of the action of azaserine on the rat pancreas by raw soy bean flour, Cancer Letters, 3:87–90.CrossRefGoogle Scholar
  26. 26.
    Newberne, P.M. and Fox, J.G., 1980, Nutritional adequacy and quality control of rodent diets, Lab. Anim. Sci., 30:352–363.Google Scholar
  27. 27.
    Pour, P.M., Runge, R.G., Birt, D., Gingell, R., Lawson, T., Nagel, D., Wallcave, L. and Salmasi, S.Z., 1981, Current knowledge of pancreatic carcinogenesis in the hamster and its relevance to the human disease, Cancer, 47:1573–1587.CrossRefGoogle Scholar
  28. 28.
    Pugh, T.D., King, J.H., Koen, H., Nychka, D., Chover, J., Wahba, G., He, Y. and Goldfarb, S., 1983, Reliable stereological method for estimating the number of microscopic hepatocellular foci from their transections, Cancer Res., 43:1261–1268.Google Scholar
  29. 29.
    Rackis, J.J., 1965, Physiological properties of soybean trypsin inhibitors and their relationship to pancreatic hypertrophy and growth inhibition of rats, Fed. Proc., 24: 1488–1493.Google Scholar
  30. 30.
    Rao, M.S., Upton, M.P., Subbarao, V. and Scarpelli, D.G., 1982, Two populations of cells with differing proliferative capacities in atypical acinar cell foci induced by 4-Hydroxyaminoquinoline-1-oxide in the rat pancreas, Lab. Invest., 46:527–534.Google Scholar
  31. 31.
    Roebuck, B.D., Baumgartner, K.J. and Thron, C.D., 1984, Characterization of two populations of pancreatic atypical acinar cell foci induced by azaserine in the rat, Lab. Invest., 50:141–l46.Google Scholar
  32. 32.
    Roebuck, B.D., Baumgartner, K.J., Thron, C.D. and Longnecker, D.S., 1984, Inhibition by retinoids of the growth of azaserine-induced foci in the rat pancreas, J. Natl. Cancer Inst., 73:233–236.Google Scholar
  33. 33.
    Roebuck, B.D., Kaplita, P.V. and Baumgartner, K.J., 1985, Enhancement of pancreatic carcinogenesis by raw soybean protein isolate, Fed. Proc., 44:xii.Google Scholar
  34. 34.
    Roebuck, B.D. and Longnecker, D.S., 1977, Species and rat strain variation in pancreatic nodule induction by azaserine, J. Natl. Cancer Inst., 59:1273–1277.Google Scholar
  35. 35.
    Roebuck, B.D. and Longnecker, D.S., 1979, Response of two rodents, Mastomys natalensis and Mystromys albicaudatus, to the pancreatic carcinogen azaserine, J. Natl. Cancer Inst., 62:1269–1271.Google Scholar
  36. 36.
    Roebuck, B.D. and Longnecker, D.S., 1983, Dietary lipid promotion of azaserine-induced pancreatic tumors in the rat, in: “Diet, Nutrition, and Cancer: From Basic Research to Policy Implications”, D.A. Roe, ed., Alan R. Liss, Inc., New York.Google Scholar
  37. 37.
    Roebuck, B.D., Longnecker, D.S., Baumgartner, K.J. and Thron, C.D., 1985, Carcinogen-Induced lesions in the rat pancreas: Effects of varying levels of essential fatty acid, Cancer Res., in press.Google Scholar
  38. 38.
    Roebuck, B.D., Longnecker, D.S. and Yager, J.D., 1983, Initiation and promotion in pancreatic carcinogenesis, in: “Mechanisms of Tumor Promotion. Vol. 1. Tumor Promotion in Internal Organs”, T.J. Slaga, ed., CRC Press, Inc., Boca Raton, FL.Google Scholar
  39. 39.
    Roebuck, B.D., MacMillan, D.L., Bush, D.M. and Kensler, T.W., 1984, Modulation of azaserine-induced pancreatic foci by phenolic antioxidants, J. Natl. Cancer Inst., 72:1405–1410.Google Scholar
  40. 40.
    Roebuck, B.D., Yager, J.D. and Longnecker, D.S., 1981, Dietary modulation of azaserine-induced pancreatic carcinogenesis in the rat. Cancer Res., 41:888–893.Google Scholar
  41. 41.
    Roebuck, B.D., Yager, J.D., Longnecker, D.S. and Wilpone, S.A., 1981, Promotion by unsaturated fat of azaserine-induced pancreatic carcinogneesis in the rat, Cancer Res., 41:3961–3966.Google Scholar
  42. 42.
    Rowlatt, U.F., 1967, Pancreatic neoplasms of rats and mice, in: “Pathology of Laboratory Rats and Mice”, F.J.C. Roe, ed., Blackwell Scientific Publications, Oxford.Google Scholar
  43. 43.
    Ryser, H.J.-P., 1971, Chemical carcinogenesis, New Engl. J. Med., 285: 721–734.CrossRefGoogle Scholar
  44. 44.
    Scarpelli, D.G., Rao, S.M. and Reddy, J.K., 1984, Studies of pancreatic carcinogenesis in different animal models, Environ. Health Prospect., 56:219–227.CrossRefGoogle Scholar
  45. 45.
    Slaga, T.J. (ed.), 1983, “Mechanisms of Tumor Promotion. Vol. I. Tumor Promotion in Internal Organs”, CRC Press, Inc., Boca Raton, FL.Google Scholar
  46. 46.
    Struthers, B.J., MacDonald, J.R., Dahlgren, R.R. and Hopkins, D.T., 1983, Effects on the moneky, pig and rat pancreas of soy products with varying levels of trypsin inhibitor and comparison with the administration of cholecystokinin, J. Nutr., 113:86–97.Google Scholar
  47. 47.
    Temler, R.S., Dormond, C.A., Simon, E., Morel, B. and Mettraux, C., 1984, Response of rat proteases to dietary proteins, their hydrolysates and soybean trypsin inhibitor, J. Nutr., 114:270–278.Google Scholar
  48. 48.
    Tove, S.B., 1981, Working group V: Hormones, fat, and cancer. Report and recommendations, Cancer Res., 41:3824Google Scholar
  49. 49.
    Weast, R.C. (ed.), 1968, “Handbook of Chemistry and Physics, 49th Edition”, The Chemical Rubber Company, Cleveland, OH.Google Scholar
  50. 50.
    Yager, J.D., Roebuck, B.D., Zurlo, J., Longnecker, D.S., Weselcouch, E.O. and Wilpone, S.A., 1981, Rationale for a single-dose azaserine protocol for initiation of pancreatic carcinogenesis in the rat, Int. J. Cancer, 28:601–606.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • B. D. Roebuck
    • 1
  1. 1.Department of Pharmacology and ToxicologyDartmouth Medical SchoolHanoverUSA

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