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Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N ′-nitro-N-nitrosoguanidine in Wistar rats
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  • Regular Article
  • Open access
  • Published: 29 January 1999

Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N ′-nitro-N-nitrosoguanidine in Wistar rats

  • M Tatsuta1,
  • H Iishi1,
  • M Baba1,
  • R Hirasawa1,
  • H Yano1,
  • N Sakai1 &
  • …
  • A Nakaizumi1 

British Journal of Cancer volume 79, pages 732–736 (1999)Cite this article

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Summary

The effect of prolonged administration of all-trans-retinoic acid (RA) on sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine, and the labelling and apoptotic indices and immunoreactivity of transforming growth factor (TGF) α in the gastric cancers was investigated in Wistar rats. After 25 weeks of carcinogen treatment, the rats were given chow pellets containing 10% sodium chloride and subcutaneous injections of RA at doses of 0.75 or 1.5 mg kg–1body weight every other day. In week 52, oral supplementation with sodium chloride significantly increased the incidence of gastric cancers compared with the untreated controls. Long-term administration of RA at both doses significantly reduced the incidence of gastric cancers, which was enhanced by oral administration of sodium chloride. RA at both doses significantly decreased the labelling index and TGF-α immunoreactivity of gastric cancers, which were enhanced by administration of sodium chloride, and significantly increased the apoptotic index of cancers, which was lowered by administration of sodium chloride. These findings suggest that RA attenuates gastric carcinogenesis, enhanced by sodium chloride, by increasing apoptosis, decreasing DNA synthesis, and reducing TGF-α expression in gastric cancers.

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    This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication

References

  • De Larco, J. E. & Todaro, G. J. (1978). Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci USA 75: 4001–4005.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Delia, D., Aiello, A., Lombardi, L., Pelicci, P. G., Grignani, F., Formelli, F., Menard, S., Costa, A., Veronesi, U. & Pierotti, M. A. (1993). N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res 53: 6036–6041.

    CAS  PubMed  Google Scholar 

  • Derynck, R. (1986). Transforming growth factor-alpha: structure and biological activities. J Cell Biochem 32: 293–304.

    Article  CAS  PubMed  Google Scholar 

  • Gratzner, H. G. (1982). Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: a new reagent for detection of DNA replication. Science 218: 474–475.

    Article  CAS  PubMed  Google Scholar 

  • Jetten, A. M., Kim, J. S., Sacks, P. G., Rearick, J. I., Lotan, D., Hong, W. K. & Lotan, R. (1990). Suppression of growth and squamous cell differentiation markers in cultured human head and neck squamous carcinoma cells by beta-all-transretinoic acid. Int J Cancer 45: 195–202.

    Article  CAS  PubMed  Google Scholar 

  • Liaudet-Coopman, E. D. E., Berchem, G. J. & Wellstein, A. (1997). Inhibition of angiogenesis and induction of apoptosis by retinoic acid in squamous cell carcinoma. Clin Cancer Res 3: 179–184.

    CAS  PubMed  Google Scholar 

  • Lippman, S. M., Kessler, J. F. & Meyskens, F. L. (1987). Retinoids as preventive and therapeutic anticancer agents. Cancer Treat Rep 71: 391–405 (part I), 493–515 (part II).

    CAS  PubMed  Google Scholar 

  • Livingstone, J. I., Filipe, M. I. & Wastell, C. (1994). Expression of transforming growth factor alpha in experimental gastric carcinogenesis. Gut 35: 604–607.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lotan, R. (1994). Suppression of squamous cell carcinoma growth and differentiation by retinoids. Cancer Res 54: 1987s–1990s.

    CAS  PubMed  Google Scholar 

  • McGeady, M. L., Kerby, S., Shanker, V., Ciardiello, F., Salomon, D. & Seidman, M. (1989). Infection with a TGF-alpha retroviral vector transforms normal mouse mammary epithelial cells but not normal rat fibroblasts. Oncogene 4: 1375–1385.

    CAS  PubMed  Google Scholar 

  • Miller, R. G. (1966). Simultaneous Statistical Inference, McGraw-Hill: New York

    Google Scholar 

  • Miller, L. A., Zhao, Y. H. & Wu, R. (1996). Inhibition of TGF-α gene expression by vitamin A in airway epithelium. J Clin Invest 97: 1429–1435.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morstyn, G., Hsu, S. M., Kinsella, T., Gratzner, H., Russo, A. & Mitchell, J. B. (1983). Bromodeoxyuridine in tumors and chromosomes detected with monoclonal antibody. J Clin Invest 72: 1844–1850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ponzoni, M., Bocca, P., Chiesa, V., Decensi, A., Pistoia, V., Raffaghello, L., Rozzo, C. & Montaldo, P. G. (1995). Differential effects of N-(4-hydroxyphenyl)retinamide and retinoic acid on neuroblastoma cells: apoptosis versus differentiation. Cancer Res 55: 853–861.

    CAS  PubMed  Google Scholar 

  • Shankar, V., Ciardiello, F., Kim, N., Derynck, R., Liscia, D. S., Merlo, G., Langton, B. C., Sheer, D., Callahan, R. & Bassin, R. H. (1989). Transformation of an established mouse mammary epithelial cell line following transfection with a human transforming growth factor alpha cDNA. Carcinogenesis 2: 1–11.

    Article  CAS  Google Scholar 

  • Shirai, T., Fukushima, S., Ohshima, M., Masuda, A. & Ito, N. (1984). Effect of butylated hydroxyanisole, butylated hydroxytoluene, and NaCl on gastric carcinogenesis initiated with N-methyl-N′-nitro-N-nitrosoguanidine in F344 rats. J Natl Cancer Inst 72: 1189–1198.

    CAS  PubMed  Google Scholar 

  • Takahashi, M., Kokuba, T., Furukawa, T., Kurokawa, Y. & Hayashi, Y. (1984). Effect of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N′-nitro-N-nitrosoguanidine. Gann 75: 494–501.

    CAS  PubMed  Google Scholar 

  • Tatsuta, M., Iishi, H., Yamamura, H., Baba, M., Yamamoto, R. & Taniguchi, H. (1988). Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res 48: 1591–1595.

    CAS  PubMed  Google Scholar 

  • Tatsuta, M., Iishi, H., Baba, M., Yano, H., Uehara, H. & Nakaizumi, A. (1995). Ornithine decarboxylase inhibitor attenuates NaCl enhancement of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine. Carcinogenesis 16: 2107–2110.

    Article  CAS  PubMed  Google Scholar 

  • Tatsuta, M., Iishi, H., Baba, M., Uehara, H., Nakaizumi, A. & Iseki, K. (1997). Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet. Cancer Lett 116: 247–252.

    Article  CAS  PubMed  Google Scholar 

  • Tatsuta, M., Iishi, H., Baba, M., Hirasawa, R., Iseki, K., Yano, H., Sakai, N., Uehara, H. & Nakaizumi, A. (1998). Inhibition by transforming growth factor (34–43)-α, a TGF-α antagonist, of gastric carcinogenesis induced by N-methyl-N′-nitro-N-nitrosoguanidine in Wistar rats. Br J Cancer 78: 857–861.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Toma, S., Isnardi, L., Raffo, P., Dastoli, G., DeFrancisci, E., Riccardi, L., Palumbo, R. & Bollag, W. (1997). Effects of all-trans-retinoic acid and 13-cis-retinoic acid on breast cancer cell lines: growth inhibition and apoptosis induction. Int J Cancer 70: 619–627.

    Article  CAS  PubMed  Google Scholar 

  • Törmänen, U., Eerola, A-K, Painio, P., Vähäkangas, K., Soini, Y., Sormunen, R., Bloigu, R., Lehto, V-P & Pääkkö, P. (1995). Enhanced apoptosis predicts shortened survival in non-small-cell lung carcinoma. Cancer Res 55: 5595–5602.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, 537-8511, Japan

    M Tatsuta, H Iishi, M Baba, R Hirasawa, H Yano, N Sakai & A Nakaizumi

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  2. H Iishi
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From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/

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Tatsuta, M., Iishi, H., Baba, M. et al. Attenuation by all-trans-retinoic acid of sodium chloride-enhanced gastric carcinogenesis induced by N-methyl-N ′-nitro-N-nitrosoguanidine in Wistar rats. Br J Cancer 79, 732–736 (1999). https://doi.org/10.1038/sj.bjc.6690117

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  • Received: 06 April 1998

  • Revised: 13 July 1998

  • Accepted: 16 July 1998

  • Published: 29 January 1999

  • Issue date: 01 February 1999

  • DOI: https://doi.org/10.1038/sj.bjc.6690117

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Keywords

  • all-trans-retinoic acid
  • sodium chloride
  • gastric carcinogenesis
  • transforming growth factor α
  • apoptosis

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