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Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane

Published online by Cambridge University Press:  01 August 2008

G. Brozovic ,
N. Orsolic ,
F. Knezevic ,
A. Horvat Knezevic ,
V. Benkovic ,
D. V. Vrdoljak  and
A. Saric
G. Brozovic*
Affiliation:
University Hospital for Tumours, Department of Anaesthesiology and ICU, Zagreb, Croatia
N. Orsolic
Affiliation:
University of Zagreb, Faculty of Science, Department of Animal Physiology, Zagreb, Croatia
F. Knezevic
Affiliation:
University Hospital for Tumours, Department of Pathology, Zagreb, Croatia
A. Horvat Knezevic
Affiliation:
University of Zagreb, Faculty of Science, Department of Animal Physiology, Zagreb, Croatia
V. Benkovic
Affiliation:
University of Zagreb, Faculty of Science, Department of Animal Physiology, Zagreb, Croatia
D. V. Vrdoljak
Affiliation:
University Hospital for Tumours, Department of Surgical Oncology, Zagreb, Croatia
A. Saric
Affiliation:
Rudjer Boskovic Institute, Zagreb, Croatia
*
Correspondence to: Gordana Brozovic, Department of Anaesthesiology and ICU, University Hospital for Tumors, Ilica 197, HR-10 000 Zagreb, Croatia. E-mail: gordana.brozovic@kzt.hr; Tel: +385 1 37 83552; Fax: +385 1 37 75536
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Summary

Background and objective

The influence of the combined application of cisplatin and sevoflurane on a variety of cell types of healthy mice or mice bearing Ehrlich ascites tumour has been investigated in an in vivo study.

Methods

The alkaline comet assay method was carried out on peripheral blood leucocytes, brain, liver, kidney and tumour cells of healthy mice or mice bearing Ehrlich ascites tumour. Groups of mice were treated intraperitoneally with cisplatin, exposed to sevoflurane or by combined treatment of sevoflurane after treatment with cisplatin for 3 consecutive days.

Results

The in vivo exposure to sevoflurane induced genotoxicity to all assayed cells. A strong synergistic genotoxic effect to peripheral blood leucocytes, liver and kidney cells was found in mice receiving both cisplatin and sevoflurane. In contrast, a decrease of the comet tail lengths of brain cells in the combined treatments was found as compared to cisplatin alone in both healthy (P < 0.001) and Ehrlich ascites tumour-bearing mice (P < 0.05), respectively. In addition, Ehrlich ascites tumour cells of mice treated with combined treatments showed a decrease in tail lengths (P < 0.001). These findings indicate an antagonistic effect of combined treatments.

Conclusion

Treatment of mice with cisplatin and sevoflurane induced genotoxic effect in peripheral blood leucocytes, liver, kidney, brain and Ehrlich ascites tumour cells; synergistic effect of combined treatments was expressed in all cells but brain and Ehrlich ascites tumour cells.

Keywords

SEVOFLURANECISPLATINMUTAGENICITY TESTS; COMET ASSAYMICE
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 8 , August 2008 , pp. 642 - 647
Copyright
Copyright © European Society of Anaesthesiology 2008

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