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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: [email protected]; 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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References

1.Kvolik, S, Glavas-Obrovac, L, Sakic, K, Margaretic, D, Karner, I. Anaesthetic implications of anticancer chemotherapy. Eur J Anaesthesiol 2003; 20: 1–13.CrossRefGoogle ScholarPubMed
2.Pleuvry, A. Anaesthetic relevance of drugs used to treat cancer. Anaesth Intensive Care Med 2006; 7 (6): 189–192.CrossRefGoogle Scholar
3.Hegarty, M, Chisholm, D. Chemotherapy and anaesthesia. Curr Anaesth Crit Care 2002; 13: 168–174.CrossRefGoogle Scholar
4.Madias, NE, Harrington, JT. Platinum nephrotoxicity. Am J Med 1978; 65: 307–314.CrossRefGoogle ScholarPubMed
5.Cersosimo, RJ. Hepatotoxicity associated with cisplatin chemotherapy. Ann Pharmacother 1993; 27: 438–441.CrossRefGoogle ScholarPubMed
6.Şardaş, S, Aygün, N, Gamli, M et al. Use of alkaline Comet assay (single cell gel electrophoresis technique) to detect DNA damages in lymphocytes of operating room personnel occupationally exposed to anaesthetic gases. Mutat Res 1998; 418: 93–100.CrossRefGoogle ScholarPubMed
7.Sardas, S, Izdes, S, Ozcagli, E, Kanbak, O, Kadioglu, E. The role of antioxidant supplementation in occupational exposure to waste anaesthetic gases. Int Arch Occup Environ Health 2006; 80: 154–159.CrossRefGoogle ScholarPubMed
8.Kvolik, S, Glavas-Obrovac, L, Bares, V, Karner, I. Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines. Life Sci 2005; 77: 2369–2383.CrossRefGoogle ScholarPubMed
9.Karabiyik, L, Şardaş, S, Polat, U, KocabaŞ, NA, Karakaya, AE. Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using the comet assay. Mutat Res 2001; 492: 99–107.CrossRefGoogle ScholarPubMed
10.Szyfter, K, Szulc, R, Mikstacki, A, Stachecki, I, Rydzanicz, M, Jaloszyński, P. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet 2004; 45: 369–374.Google ScholarPubMed
11.Hack, G, Karzel, K. Suspension cultures of Ehrlich ascites tumor cells test system for the study of cytotoxic effects of anaesthetics. Anaesthesist 1981; 30: 88–94.Google Scholar
12.Hack, G, Karzel, K, Panthong, A, Stein, P. In vitro studies on the influence of volatile anaesthetics on cell number, cell volume, and cellular protein, DNA, and RNA content. Anaesthesist 1981; 30: 134–143.Google ScholarPubMed
13.Singh, NP, Mc Coy, MT, Tice, RR, Schneider, EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988; 175: 184–191.CrossRefGoogle ScholarPubMed
14.McKelvey-Martin, VJ, Green, MHL, Schmezer, P, Pool-Zobel, BL, De Meo, MP, Collins, A. The single cell gel electrophoresis assay (comet assay): a European review. Mutat Res 1993; 288: 47–63.CrossRefGoogle ScholarPubMed
15.Collins, AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol 2004; 26: 249–261.CrossRefGoogle ScholarPubMed
16.Hartmann, A, Agurell, E, Beevers, C et al. Recommendations for conducting the in vivo alkaline Comet assay. Mutagenesis 2003; 18: 45–51.CrossRefGoogle ScholarPubMed
17.Kopjar, N, Garaj-Vrhovac, V, Milas, I. Assessment of chemotherapy-induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay. Teratog Carcinog Mutagen 2002; 22: 13–30.CrossRefGoogle ScholarPubMed
18.Fillastre, JP, Raguenez-Viotte, G. Cisplatin nephrotoxicity. Toxicol Lett 1989; 46: 163–175.CrossRefGoogle ScholarPubMed
19.Lee, HT, Kim, M, Jan, M, Emala, CW. Anti-inflammatory and antinecrotic effects of the volatile anesthetic sevoflurane in kidney proximal tubule cells. Am J Physiol Renal Physiol 2006; 291: 67–78.CrossRefGoogle ScholarPubMed
20.Lee, HT, Ota-Setlik, A, Fu, Y, Nasr, SH, Emala, CW. Differential protective effects of volatile anesthetics against renal ischemia-reperfusion injury in vivo. Anesthesiology 2004; 101: 1313–1324.CrossRefGoogle ScholarPubMed
21.Jaloszyński, P, Tądrowska, M, Kujawski, M, Wąsowicz, M, Szulc, R, Szyfter, K. Genotoxicity of inhalation anesthetics (halothane, isoflurane and sevoflurane) in human lymphocytes studied in vivo and in vitro. Neoplasma 1999; 46: 20–22.Google Scholar
22.Reichle, FM, Conzen, PF. Halogenated inhalational anaesthetics. Best Pract Res Clin Anaesthesiol 2003; 17: 29–46.CrossRefGoogle ScholarPubMed
23.Wozniak, K, Czechowska, A, Blasiak, J. Cisplatin-evoked DNA fragmentation in normal and cancer cells and its modulation by free radical scavengers and the tyrosine kinase inhibitor STI571. Chem Biol Int 2004; 147: 309–318.CrossRefGoogle ScholarPubMed