Protective Effect of Soybean against Hepatocarcinogenesis Induced by DL-Ethionine

  • Aiad, Fatma (Department of Cancer Biology, National Cancer Institute, Cairo University) ;
  • El-Gamal, Basiouny (Department of Biochemistry, Faculty of Science, Alexandria University) ;
  • Al-Meer, Jehan (Department of Chemistry, Faculty of Science, Qatar University) ;
  • El-Kerdasy, Zinab (Department of Cancer Biology, National Cancer Institute, Cairo University) ;
  • Zakhary, Nadia (Department of Cancer Biology, National Cancer Institute, Cairo University) ;
  • El-Aaser, Abdelbaset (Department of Cancer Biology, National Cancer Institute, Cairo University)
  • Published : 2004.05.31


There has been increasing interest in the value of using soybean to delay or reduce the tumor incidence. This study was undertaken to investigate the possible protective effects of soybean against hepatocarcinogenesis induced by DL-ethionine. Accordingly, we measured biochemical changes occurring in serum and liver of rats treated with DL-ethionine in the presence or absence of soybean. Male albino rats were fed a control diet containing the hepatocarcinogen, DL-ethionine, or the control diet plus soybean 30%, or the control diet plus soybean plus DL-ethionine 0.25% for three months and then returned to a control diet for up to nine months. Rats fed a control diet plus DL-ethionine showed a gradual decrease in liver DNA, RNA, total protein, and liver weight and enzyme activites of liver transaminases (GOT and GPT) and alkaline phosphatase over the 7-month study period. This was followed by a large increase in the liver parameters at the end of the $9^{th}$ month, except for 5'-nucleotidase and glucose-6-phosphatase that showed a large decrease. On the other hand, a gradual increase in the serum enzyme activities of GOT, GPT, 5-nucleotidase, alkaline phosphatase, and in the albumin/globulin (A/G) ratio is observed in the group of rats fed a control diet plus DL-ethionine compared to the control group over 8 months, and this was followed by a large increase in all serum parameters studied at nine-months. The administration of 30% soybean to the rat diet in addition to DL-ethionine maintained all parameters studied at near control values until the end of the $9^{th}$ month. This study suggests that soybean has a protective effect against the hepatocarcinogenesis induced by DL-ethionine.


  1. Akhurst, B., Croager, E. J., Farley-Roche, C. A., Ong, J. K., Dumble, M. L., Knight, B. and Yeoh, G. C. (2001) A modified choline-deficient, ethionine-supplemented diet protocol effectively induces oval cells in mouse liver. Hepatology 34, 519-522.
  2. Akl, S. M. and El-Kaabi, N. A. (1992) Effect of soybean feeding on experimental carcinogenesis. J. Egypt. Nat. Center Inst. 5, 443-471.
  3. Allen, P. T. and Poirier, L. A. (1997) Suppression by Phenobarbital of ethionine-induced hepatocellular carcinoma formation and hepatic S-adenosylethionine levels, Carcinogenesis 18, 1103-1107.
  4. Anderson, R. L. and Wolf, W. J. (1995) Compositional changes in trypsin inhibitors, phytic acid, saponins and isoflavones related to soybean processing. J. Nutr. 125, 581S-588S.
  5. Appelt, L. C. and Reicks, M. M. (1999) Soy induces phase II enzymes but does not inhibit dimethylbenz[a]anthraceneinduced carcinogenesis in female rats. J. Nutr. 129, 1820-1826.
  6. Barnes, S., Grubbs, C., Setchell, K. D. and Carlson, J. (1990) Soybeans inhibit mammary tumors in models of breast cancer. Prog. Clin. Biol. Res. 347, 239-253.
  7. Corasanti, J. B., Hobika, G. H. and Markus, G. (1982) Interference with dimethylhydrazine induction of colon tumors in mice by aminocaproic acid. Science 216, 1020-1028.
  8. Croager, E. J., Smith, P. G. and Yeoh, G. C. (2002) Ethanol interactions with a choline-deficient, ethionine-supplemented feeding regime potentiate preneoplastic cellular alterations in rat liver. Carcinogenesis 23, 1685-1693.
  9. De Duve, C., Pressman, B. C., Gianetto, O. R., Wahianx, R. and Applemans, F. (1955) Tissue fractionation studies, intracellular distribution pattern of enzymes in rat liver tissue. Biochem. J. 60, 604-613.
  10. De Lamirande, G. (1964) Protein bound dye and purine catabolizing enzymes in parenchymal and non-parenchymal cells of rats fed 4-dimethylamine-azobenzene (DAB). Cancer Res. 24, 742-750.
  11. El-Aaser, A. A. (1965) Nucleotidases and ribonucleases in liver and liver tumors. PhD thesis, London University.
  12. El-Aaser, A. A. and El-Merzabani, M. M. (1975) Simultaneous determination of 5-nucleotidase and alkaline phosphatase activities in serum. Z. Klin. Chem. Klin. Biochem. 13, 453-459.
  13. El-Aaser, A. A., Ibrahim, H. A., Abdeen, A. M. and AKL, S. A. (1986) Effect of soybean feeding on Experimental carcinogenesis. 1. Hepatocarcinogenesis by para-dimethyl aminoazobenzene (DAB) in rats fed soybean: Histopathological and histochemical studies. J. Egypt. Natl. Cancer Inst. 2, 443-453.
  14. El-Aaser, A. A., Zakhary, N. I., El-Guindy, S. M., Hafeiz, A. A., Mokhtar, N. (1994) Effect of soybean, vicia faba, and vitamin C on the carcinogenicity of DMBA. Nutr. Cance. 22, 195-200.
  15. Emmelot, P. and Bos, C. T. (1971) Studies on plasma membrane. XV. A sex difference in alkaline phosphatase activities of plasma membrane isolated from rat liver. Biochem. Biophys. Acta 249, 293-300.
  16. Hacker, H. J., Steinberg, P. and Bannasch, P. (1998) Pyruvate kinaseisoenzyme shift from L-type to M2-type is a late event in hepatocarcinogenesis induced in rats by a choline-deficient/DL-ethionine-supplemented diet. Carcinogenesis 19, 99-107.
  17. Hacker, H. J., Steinberger, P., Toshkov, I., Oesch, F., Bannasch, P. (1992) Persistence of the cholangiocellular and hepatocellular lesions observed in rats fed a choline-deficient/DL-ethioninesupplemented diet. Carcinogenesis 13, 271-276.
  18. Inbar, M., Yuli, I. and Raz, A. (1977) Contact mediated changes in the fluidity of membrane lipids in normal and malignant transformed mammalian fibroblasts. Expl. Cell. Res. 105, 325-335.
  19. Karnovsky, M. L., Lazdins, J., Drath, D. B. and Harper, H. (1975) Biochemical characteristics of activated macrophages. Ann. N. Y. Acad. Sci. 256, 266-275.
  20. Kennedy, A. R. (1995) The evidence for soybean products as cancer preventive agents. J. Nutr. 125, 733S-743S.
  21. Lamartiniere, C. A. (2000) Protection against breast cancer with genistein: a component of soy. Am. J. Clin. Nutr. 71, 1705S-1707S.
  22. Lee, K. W., Wang, H. J., Murphy, P. A. and Hendrich, S. (1995) Soybean isoflavone extract suppresses early but not later promotion of hepatocarcinogenesis by Phenobarbital in female rat liver. Nutr. Cancer 24, 267-278.
  23. Lenzi, R., Liu, M. H., Lenzen, R., Han, T., Alpini, G. and Tavoloni, N. (1991) Distribution of glucose-6-phosphatase activity in normal, hyperplastic, and preneoplastic rat liver. Virchows. Arch. B. Cell. Pathol. Incl. Mol. Pathol. 61, 279-287.
  24. Lowry, O.H., Rosenbrough, S.N. and Randell, S.R. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193, 265-275.
  25. Melmed, R. M., El-Aaser, A. A. and Holt, S. J. (1976) Hypertrophy and hyperplasia of the neonatal rat exocrine pancreas induced by orally administered soybean trypsin inhibitor. Bioch. Biophys. Acta 321, 280-288.
  26. Mejbaum, W. (1939) Uber die bestimung kleiner pentosemengen, insbesondere in derivaten der adenylasaure. Z. Physiol. Chem. 268, 117-121.
  27. Messina, M. J. (1999) Legumes and soybeans: overview of their nutritional profiles and health effects. Am. J. Clin. Nutr. 70, 439S-450S.
  28. Messina, M. and Messina, V. (1991) Increasing use of soyfoods and their potential role in cancer prevention. J. Am. Diet. Assoc. 91, 836-840.
  29. Miller, J. A. (1970) Carcinogenesis by biochemicals. An overview CHA. Clowes memorial lectures. Cancer Res. 30, 559-570.
  30. Moharram, N. Z., El-Aaser, A. A., Badr El-Din, N. K. and Ibrahim, H. A. (1989) Effect of soybean on experimental carcinogenesis. IV. Phosphatases in mice liver, histochemical study. Proc. Zool. Soc. A.R. Egypt 17, 211-226.
  31. Mokhtar, N. M., El-Aaser, A. A., El-Bolkainy, M. N., Ibrahim, H. A., Badr El-Din, N. and Moharram, N. Z. (1988) Effect of soybean feeding on experimental carcinogenesis. IIICarcinogenicity of nitrite and dibutylamine in mice: A histopathological study. Eur. J. Cancer Clin. Oncol. 24, 403-411.
  32. Novikoff, P. M., Ikeda, T., Hixon, D. C. and Yam, A. (1991) Characterization of and interactions between bile ductule cells and hepatocytes in early stages of rat hepatocarcinogenesis induced by DL-ethionine..Am. J. Pathol. 139, 1351-1368.
  33. Onozawa, M., Kawamori, T., Baba, M., Fukuda, K., Toda, T., Sato, H., Ohtani, M., Akaza, H., Sugimura, T. and Wakabayashi, K. (1999) Effects of a soybean isoflavone mixture on carcinogenesis in prostate and seminal vesicles of F344 rats. Jpn. J. Cancer Res. 90, 393-398.
  34. Pugh, T. and Goldfrab, S. (1978) Quantitative histochemical and autoradiographic studies of hepatocarcinogenesis in rats fed 2-acetylamino fluorine followed by Phenobarbital. Cancer Res. 38, 4450-4457.
  35. Radwan, A. F. (1980) Studies on the effect of soybean feeding on the biochemistry of liver during carcinogenesis. PhD thesis Fac. Med., Cairo University, Egypt.
  36. Raz, A., Collard, J. G. and Inbar, M. (1978) Decrease in 5-nucleotidase activity in malignant transformed and normal stimulated cells. Cancer Res. 38, 1258-1262.
  37. Reddy, B. C., Maeaura, Y. and Wayman, M. (1983) Effect of dietary corn barn and autohydrolyzed lignin on 2,3-dimethyl-4-aminobiphenyl induced intestinal carcinogenesis in male F344 rats. J. Natl. Cancer Inst. 71, 419-426.
  38. Reitman, S. and Frankel, S. (1957) A colorimetric method for the determination of serum glutamic oxaloacetic acid and glutamic pyruvic transaminases. Am. J. Pathol. 28, 56-63.
  39. Rroll, W., Wiesner, R., Shellabarge, C. T., Holtzman, S. and Stone, J. P. (1980) Soybean diet lowers breast tumor incidence in irradiated rats. Carcinogenesis 1, 469-475.
  40. Spencer, K. and Price, C. P. (1977) Influence of reagent quality and reaction conditions on the determination of serum albumin by the bromocresol green dye-binding method. Ann. Clin. Biochem. 14, 105-115.
  41. Su, S. J., Yeh, T. M., Lei, H. Y. and Chow, N. H. (2000) The potential of soybean foods as a chemoprevention approach for human urinary tract cancer. Clin. Cancer Res. 6, 230-236.
  42. Thiagarajan, D. G., Beenink, M. R., Bourquin, L. D. and Kavas, F. A. (1998) Prevention of precancerous colonic lesions in rats by soy flakes, soy flour, genistein, and calcium. Am. J. Clin. Nutr. 68, 1394S-1399S.
  43. Tsujiuchi, T., Kobayashi, E., Nakae, D., Mizumoto, Y., Andoh, N., Kitada, H., Ohashi, K., Fukuda, T., Kido, A. and Tsutsumi, M. (1995) Prevention by methionine of enhancement of hepatocarcinogenesis by coadministration of a choline-deficient L-amino acid-defined diet and ethionine, Jpn. J. Cancer Res. 86, 1136-1142.
  44. Webb, T. E., Stromberg, P. C., Abu-Issa, H. and Curley, R. W. Jr., Moeschberger, M. (1992) Effect of dietary soybean and licorice on the male F344 rat: an integrated study of some parameters relevant to cancer chemoprevention. Nutr. Cancer 18, 215-230.
  45. Zaizen, Y., Higuchi, Y., Matsuo, N., Shirabe, K., Tokuda, H. and Takeshita, M. (2000) Antitumor effects of soybean hypocotyls and soybeans on the mammary tumor induction by N-methyln-nitrosourea in F344 rats. Anticancer Res. 20, 1439-1444.
  46. Zakhary, N. I., Badr El-Din, N., El-Aaser, A. A., Ibrahim, H. A. and Moharram, N. Z. (1989) Effect of soybean feeding and vitamin C on experimental carcinogenesis. 5. Biochemical changes in the liver of albino mice induced by feeding nitrite and dibutylamine. J. Egypt. Natl. Cancer Inst. 4, 186-189.

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