gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Cytogenetic effects of immunosuppressive drugs in vitro and in vivo

Meeting Abstract

Suche in Medline nach

  • Vilma Frick - Allgemeine Chirurgie, Allgemein-, Viszeral-, Gefäß-, und Kinderchirurgie, Homburg/Saar
  • Claudia Rubie - Allgemeine Chirurgie, Allgemein-, Viszeral-, Gefäß-, und Kinderchirurgie, Homburg/Saar

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch714

DOI: 10.3205/11dgch714, URN: urn:nbn:de:0183-11dgch7144

Veröffentlicht: 20. Mai 2011

© 2011 Frick et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Immunosuppressive drugs are used effectively to prevent immunologic rejection after solid organ transplantation. The most serious complication among patients undergoing immunosuppressive therapy is the risk of developing cancer. To date it is unknown whether the applied drugs have mutagenic properties and thus potentially contribute to an increased cancer risk.

Materials and methods: We evaluated the mutagenic and cytotoxic effects of cyclosporine A (CyA), mycophenolate mofetil (MMF), tacrolimus (FK506) and sirolimus (Siro) in human lymphocyte cultures with special consideration given to clinically relevant blood-drug concentrations. Mutagenicity was tested by analysis of micronuclei using the well-established cytokinesis-block micronucleus assay with cytochalasin B. To evaluate cytotoxicity, the cytokinesis block proliferation index was calculated. Concentrations used ranged from 0.1-2 µg/mL for CyA, 1-20 µg/mL for MMF, 5-40 ng/mL for FK506, and 2.5-50 ng/mL for Siro. We also estimated mutagenicity and cytotoxicity in blood of kidney transplanted patients by using the above mentioned techniques.

Results: Cultures supplemented with MMF or FK506 showed higher amounts of micronuclei when compared with solvent controls at all concentrations tested. Cultures supplemented with CyA also led to a rise in micronuclei number at concentrations of 0.2 µg/mL and 0.4 µg/mL. In contrast with the other immunosuppressive drugs, Siro induced only weak mutagenic activity in the micronuclei test at its highest concentration (50 ng/mL). Cytotoxic effects were seen only in MMF-supplemented cultures at all concentrations tested (P < 0.01).

Kidney transplanted patients under immunosuppression display a broad reduction of the CBPI (P< 0,001) in comparison to healthy persons and a significant increase in MN frequency (P< 0,001).

Conclusion: All immuosuppressive drugs under investigation displayed mutagenic effects in vitro, indicating that MMF and FK506 show more mutagenic effects in vitro than CyA or Siro. Moreover, all transplanted patients exhibit higher amounts of MN and a noteworthy reduction in the CBPI compared to healthy people.