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Effect of salt on cell proliferation andN-methyl-N′-nitro-N-nitrosoguanidine penetration to proliferative cells in the forestomach of rats

  • Original Papers
  • Experimental Oncology
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Abstract

We have studied the effect of intragastric instillation of 4.5M NaCl on cell proliferation and carcinogen penetration into the forestomach of Wistar rats at different time intervals after salt exposure. Cells in the S-phase were labelled by incorporation of bromodeoxyuridine and located after immunohistochemistry.N-[3H]Methyl-N′-nitro-N-nitrosoguanidine ([3H]MNNG) was used as the carcinogen and penetration of [3H]MNNG to proliferative cells was determined by autoradiography. The number of cells in S-phase per millimetre epithelium length 12 h and 24 h after salt exposure (32.2±11.9 and 20.6±7.4) was significantly higher than in the control animals (9.4±3.6). No increase in cell proliferation occurred during the first 2 h after salt exposure. Microscopy also revealed oedema in the lamina propia. The forestomach blood flow was not influenced by the application of hypertonic saline. [3H]MNNG at a concentration of 40 μg/ml did not penetrate to the proliferative cells in the forestomach and no effect of salt pretreatment on carcinogen penetration was seen. The low penetration of [3H]MNNG to proliferative cells in the forestomach epithelium may explain why this concentration of MNNG given in drinking water over several weeks usually does not induce squamous cell carcinomas in the forestomach. The previously observed cocarcinogenic effect of salt on squamous cell cercinogenesis in the upper gastrointestinal tract could be due to the observed increase in cell proliferation after salt exposure.

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Abbreviations

[3H]MNNG:

N-[3H]methyl-N′-nitro-N-nitrosoguanidine

MNNG:

N-methyl-N′-nitro-N-nitrosoguanidine

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Authors and Affiliations

  1. Surgical Research Laboratory, Department of Surgery, University of Bergen, Haukeland Hospital, N-5021, Bergen, Norway

    Halfdan Sørbye, Hjørtur Gislason & Knut Svanes

  2. Department of Anatomy and Cell Biology, University of Bergen, Bergen, Norway

    Steinar Kvinnsland

Authors
  1. Halfdan Sørbye
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  2. Hjørtur Gislason
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  3. Steinar Kvinnsland
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  4. Knut Svanes
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Additional information

This work was supported by grants from the Norwegian Cancer Society and the Helga Semb Fund. Dr. Sørbye is a Research Fellow of the Norwegian Cancer Society

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Sørbye, H., Gislason, H., Kvinnsland, S. et al. Effect of salt on cell proliferation andN-methyl-N′-nitro-N-nitrosoguanidine penetration to proliferative cells in the forestomach of rats. J Cancer Res Clin Oncol 120, 465–470 (1994). https://doi.org/10.1007/BF01191799

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  • DOI: https://doi.org/10.1007/BF01191799

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