The gastrointestinal tract as the portal of entry for foreign macromolecules: fate of DNA and proteins (original) (raw)

Abstract

The gastrointestinal tract (GIT) of mammals is the main portal of entry for foreign DNA and proteins. We have documented the fate of orally administered DNA or protein in the GIT of the mouse. The gene for the Green Fluorescent Protein (GFP) (4.7 kb) and the genomes of bacteriophage M13 (7.25 kb) and adenovirus type 2 (Ad2; 35.9 kb) were used as test DNAs. Persistence of these DNAs in the GIT was monitored by Southern hybridization and fluorescent in situ hybridization (FISH) or by PCR. For studies on proteins, recombinant glutathione-S-transferase was fed to mice. Survival of the protein in the GIT was then assessed by Western blotting. Depending on feeding schedules and food regimens, but irrespective of mouse strain or DNA length, fragments of the GFP gene or other DNAs were detectable for up to 18 h after feeding by Southern blot analysis. The GFP DNA could be visualized by FISH in cecal epithelia. A high fiber diet reduced the time required for food to pass through the GIT, and foreign DNA was cleared more rapidly. A high fat diet or complexing of the foreign DNA with protamine or lipofectin did not extend DNA persistence times. Undegraded GST protein was detected only in foregut contents up to 30 min after feeding. At 15 and 30 min post feeding, trace amounts of GST were found in extracts of the kidney. The GIT is constantly exposed to highly recombinogenic fragments of foreign DNA and to intact foreign proteins. Our data have implications for studies on carcinogenesis and mutagenesis, and on the pathogenicity of infectious proteins such as prions.

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Acknowledgments

We are indebted to Petra Böhm for expert editorial work and to Sylvia Niczyporuk, Ylva Mende, Norbert Hochstein und Uta Zedler for help in some of the experiments. This research was supported by grants from the Bayerisches Staatsministerium für Landesentwicklung und Umweltfragen, München and the Ministerium für Wissenschaft und Forschung, Düsseldorf, Germany.

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Author notes

1. M. Palka-Santini
   Present address: Institute of Medical Microbiology, University of Cologne, 50931, Cologne, Germany

Authors and Affiliations

1. Institute of Genetics, University of Cologne, 50931, Cologne, Germany
   M. Palka-Santini, B. Schwarz-Herzke, M. Hösel, D. Renz, S. Auerochs & W. Doerfler
2. Institute of Clinical and Molecular Virology, University of Erlangen-Nürnberg, 91054, Erlangen, Germany
   B. Schwarz-Herzke, M. Hösel, S. Auerochs, H. Brondke & W. Doerfler

Authors

1. M. Palka-Santini
2. B. Schwarz-Herzke
3. M. Hösel
4. D. Renz
5. S. Auerochs
6. H. Brondke
7. W. Doerfler

Corresponding author

Correspondence toW. Doerfler.

Additional information

Communicated by W. Goebel

The first two authors contributed equally to this work

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Palka-Santini, M., Schwarz-Herzke, B., Hösel, M. et al. The gastrointestinal tract as the portal of entry for foreign macromolecules: fate of DNA and proteins.Mol Genet Genomics 270, 201–215 (2003). https://doi.org/10.1007/s00438-003-0907-2

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• Received: 24 April 2003
• Accepted: 24 July 2003
• Published: 23 August 2003
• Issue date: November 2003
• DOI: https://doi.org/10.1007/s00438-003-0907-2

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