Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Feb;79(5-6):732–736. doi: 10.1038/sj.bjc.6690117

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

M Tatsuta 1, H Iishi 1, M Baba 1, R Hirasawa 1, H Yano 1, N Sakai 1, A Nakaizumi 1
PMCID: PMC2362689  PMID: 10070861

Abstract

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−1 body 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. © 1999 Cancer Research Campaign

Keywords: all-trans-retinoic acid, sodium chloride, gastric carcinogenesis, transforming growth factor α, apoptosis

Full Text

The Full Text of this article is available as a PDF (69.1 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Delia D., Aiello A., Lombardi L., Pelicci P. G., Grignani F., Grignani F., Formelli F., Menard S., Costa A., Veronesi U. N-(4-hydroxyphenyl)retinamide induces apoptosis of malignant hemopoietic cell lines including those unresponsive to retinoic acid. Cancer Res. 1993 Dec 15;53(24):6036–6041. [PubMed] [Google Scholar]
  2. Derynck R. Transforming growth factor-alpha: structure and biological activities. J Cell Biochem. 1986;32(4):293–304. doi: 10.1002/jcb.240320406. [DOI] [PubMed] [Google Scholar]
  3. Gratzner H. G. Monoclonal antibody to 5-bromo- and 5-iododeoxyuridine: A new reagent for detection of DNA replication. Science. 1982 Oct 29;218(4571):474–475. doi: 10.1126/science.7123245. [DOI] [PubMed] [Google Scholar]
  4. Jetten A. M., Kim J. S., Sacks P. G., Rearick J. I., Lotan D., Hong W. K., Lotan R. Inhibition of growth and squamous-cell differentiation markers in cultured human head and neck squamous carcinoma cells by beta-all-trans retinoic acid. Int J Cancer. 1990 Jan 15;45(1):195–202. doi: 10.1002/ijc.2910450135. [DOI] [PubMed] [Google Scholar]
  5. Liaudet-Coopman E. D., Berchem G. J., Wellstein A. In vivo inhibition of angiogenesis and induction of apoptosis by retinoic acid in squamous cell carcinoma. Clin Cancer Res. 1997 Feb;3(2):179–184. [PubMed] [Google Scholar]
  6. Lippman S. M., Kessler J. F., Meyskens F. L., Jr Retinoids as preventive and therapeutic anticancer agents (Part II). Cancer Treat Rep. 1987 May;71(5):493–515. [PubMed] [Google Scholar]
  7. Livingstone J. I., Filipe M. I., Wastell C. Expression of transforming growth factor alpha in experimental gastric carcinogenesis. Gut. 1994 May;35(5):604–607. doi: 10.1136/gut.35.5.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Lotan R. Suppression of squamous cell carcinoma growth and differentiation by retinoids. Cancer Res. 1994 Apr 1;54(7 Suppl):1987s–1990s. [PubMed] [Google Scholar]
  9. McGeady M. L., Kerby S., Shankar V., Ciardiello F., Salomon D., Seidman M. Infection with a TGF-alpha retroviral vector transforms normal mouse mammary epithelial cells but not normal rat fibroblasts. Oncogene. 1989 Nov;4(11):1375–1382. [PubMed] [Google Scholar]
  10. Miller L. A., Zhao Y. H., Wu R. Inhibition of TGF-alpha gene expression by vitamin A in airway epithelium. J Clin Invest. 1996 Mar 15;97(6):1429–1435. doi: 10.1172/JCI118564. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Morstyn G., Hsu S. M., Kinsella T., Gratzner H., Russo A., Mitchell J. B. Bromodeoxyuridine in tumors and chromosomes detected with a monoclonal antibody. J Clin Invest. 1983 Nov;72(5):1844–1850. doi: 10.1172/JCI111145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ponzoni M., Bocca P., Chiesa V., Decensi A., Pistoia V., Raffaghello L., Rozzo C., Montaldo P. G. Differential effects of N-(4-hydroxyphenyl)retinamide and retinoic acid on neuroblastoma cells: apoptosis versus differentiation. Cancer Res. 1995 Feb 15;55(4):853–861. [PubMed] [Google Scholar]
  13. Shankar V., Ciardiello F., Kim N., Derynck R., Liscia D. S., Merlo G., Langton B. C., Sheer D., Callahan R., Bassin R. H. Transformation of an established mouse mammary epithelial cell line following transfection with a human transforming growth factor alpha cDNA. Mol Carcinog. 1989;2(1):1–11. doi: 10.1002/mc.2940020102. [DOI] [PubMed] [Google Scholar]
  14. Shirai T., Fukushima S., Ohshima M., Masuda A., Ito N. Effects 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. 1984 May;72(5):1189–1198. [PubMed] [Google Scholar]
  15. Takahashi M., Kokubo T., Furukawa F., Kurokawa Y., Hayashi Y. Effects of sodium chloride, saccharin, phenobarbital and aspirin on gastric carcinogenesis in rats after initiation with N-methyl-N'-nitro-N-nitrosoguanidine. Gan. 1984 Jun;75(6):494–501. [PubMed] [Google Scholar]
  16. Tatsuta M., Iishi H., Baba M., Hirasawa R., Iseki K., Yano H., Sakai N., Uehara H., Nakaizumi A. Inhibition by transforming growth factor (34-43)-alpha, a TGF-alpha antagonist, of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Br J Cancer. 1998 Oct;78(7):857–861. doi: 10.1038/bjc.1998.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tatsuta M., Iishi H., Baba M., Uehara H., Nakaizumi A., Iseki K. Reduction in NaCl-enhanced gastric carcinogenesis in rats fed a high-protein diet. Cancer Lett. 1997 Jun 24;116(2):247–252. doi: 10.1016/s0304-3835(97)00197-3. [DOI] [PubMed] [Google Scholar]
  18. Tatsuta M., Iishi H., Baba M., Yano H., Uehara H., Nakaizumi A. Ornithine decarboxylase inhibitor attenuates NaCl enhancement of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. Carcinogenesis. 1995 Sep;16(9):2107–2110. doi: 10.1093/carcin/16.9.2107. [DOI] [PubMed] [Google Scholar]
  19. Tatsuta M., Iishi H., Yamamura H., Baba M., Yamamoto R., Taniguchi H. Effect of cimetidine on inhibition by tetragastrin of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. Cancer Res. 1988 Mar 15;48(6):1591–1595. [PubMed] [Google Scholar]
  20. Toma S., Isnardi L., Raffo P., Dastoli G., De Francisci E., Riccardi L., Palumbo R., Bollag W. Effects of all-trans-retinoic acid and 13-cis-retinoic acid on breast-cancer cell lines: growth inhibition and apoptosis induction. Int J Cancer. 1997 Mar 4;70(5):619–627. doi: 10.1002/(sici)1097-0215(19970304)70:5<619::aid-ijc21>3.0.co;2-6. [DOI] [PubMed] [Google Scholar]
  21. Törmänen U., Eerola A. K., Rainio P., Vähäkangas K., Soini Y., Sormunen R., Bloigu R., Lehto V. P., Päkkö P. Enhanced apoptosis predicts shortened survival in non-small cell lung carcinoma. Cancer Res. 1995 Dec 1;55(23):5595–5602. [PubMed] [Google Scholar]
  22. de Larco J. E., Todaro G. J. Growth factors from murine sarcoma virus-transformed cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):4001–4005. doi: 10.1073/pnas.75.8.4001. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES