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The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice

  • Animal Genetics ∙ Original Paper
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Abstract

The aim of this study was to evaluate the genotoxicity of repeated exposure to isoflurane or halothane and compare it with the genotoxicity of repeated exposure to cisplatin. We also determined the genotoxicity of combined treatment with inhalation anaesthetics and cisplatin on peripheral blood leucocytes (PBL), brain, liver and kidney cells of mice. The mice were divided into six groups as follows: control, cisplatin, isoflurane, cisplatin–isoflurane, halothane and cisplatin–halothane, and were exposed respectively for three consecutive days. The mice were treated with cisplatin or exposed to inhalation anaesthetic; the combined groups were exposed to inhalation anaesthetic after treatment with cisplatin. The alkaline comet assay was performed. All drugs had a strong genotoxicity (P < 0.05 vs. control group) in all of the observed cells. Isoflurane caused stronger DNA damage on the PBL and kidney cells, in contrast to halothane, which had stronger genotoxicity on brain and liver cells. The combination of cisplatin and isoflurane induced lower genotoxicity on PBL than isoflurane alone (P < 0.05). Halothane had the strongest effect on brain cells, but in the combined treatment with cisplatin, the effect decreased to the level of cisplatin alone. Halothane also induced the strongest DNA damage of the liver cells, while the combination with cisplatin increased its genotoxicity even more. The genotoxicity of cisplatin and isoflurane on kidney cells were nearly at the same level, but halothane caused a significantly lower effect. The combinations of inhalation anaesthetics with cisplatin had stronger effects on kidney cells than inhalation anaesthetics alone. The observed drugs and their combinations induced strong genotoxicity on all of the mentioned cells.

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References

  • Alleva R, Tomasetti M, Solenghi MD, Stagni F, Gamberini F, Bassi A, Fornasari PM, Fanelli G, Borghi B (2003) Lymphocyte DNA damage precedes DNA repair or cell death after orthopaedic surgery under general anaesthesia. Mutagenesis 18:423–428

    Article  PubMed  CAS  Google Scholar 

  • Aly MS, Ashour MB, El Nahas SM, Abo Zeid MAF (2003) Genotoxicity and cytotoxicity of the anticancer drugs gemcitabine and cisplatin, separately and in combination: in vivo studies. J Biol Sci 3:961–972

    Article  Google Scholar 

  • Brozovic G, Orsolic N, Knezevic F, Horvat Knezevic A, Benkovic V, Vrdoljak DV, Saric A (2008) Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane. Eur J Anaesthesiol 25:642–647

    Article  PubMed  CAS  Google Scholar 

  • Brozovic G, Orsolic N, Knezevic F, Horvat Knezevic A, Benkovic V, Sakic K, Hrgovic Z, Bendelja K, Fassbender WJ (2009) Genotoxicity and cytotoxicity of cisplatin treatment combined with anaesthetics on EAT cells in vivo. Onkologie 32:337–343

    Article  PubMed  CAS  Google Scholar 

  • Crul M, van Waardenburg RC, Beijnen JH, Schellens JH (2002) DNA-based drug interactions of cisplatin. Cancer Treat Rev 28:291–303

    Article  PubMed  CAS  Google Scholar 

  • Franks NP, Lieb WR (2004) Seeing the light: protein theories of general anesthesia. 1984. Anesthesiology 101:235–237

    Article  PubMed  CAS  Google Scholar 

  • Hegarty M, Chisholm D (2002) Chemotherapy and anaesthesia. Curr Anaesth Crit Care 13:168–174

    Article  Google Scholar 

  • Jaloszyński P, Kujawski M, Wasowicz M, Szulc R, Szyfter K (1999) Genotoxicity of inhalation anesthetics halothane and isoflurane in human lymphocytes studied in vitro using the comet assay. Mutat Res 439:199–206

    PubMed  Google Scholar 

  • Jirsova K, Mandys V, Gispen WH, Bär PR (2006) Cisplatin-induced apoptosis in cultures of human Schwann cells. Neurosci Lett 392:22–26

    Article  PubMed  CAS  Google Scholar 

  • Karpiński TM, Kostrzewska-Poczekaj M, Stachecki I, Mikstacki A, Szyfter K (2005) Genotoxicity of the volatile anaesthetic desflurane in human lymphocytes in vitro, established by comet assay. J Appl Genet 46:319–324

    PubMed  Google Scholar 

  • Kaymak C, Kadioglu E, Basar H, Sardas S (2004) Genoprotective role of vitamin E and selenium in rabbits anaesthetized with sevoflurane. Hum Exp Toxicol 23:413–419

    Article  PubMed  CAS  Google Scholar 

  • Kvolik S, Glavas-Obrovac L, Bares V, Karner I (2005) Effects of inhalation anesthetics halothane, sevoflurane, and isoflurane on human cell lines. Life Sci 77:2369–2383

    Article  PubMed  CAS  Google Scholar 

  • Kvolik S, Glavas-Obrovac L, Sakic K, Margaretic D, Karner I (2003) Anaesthetic implications of anticancer chemotherapy. Eur J Anaesthesiol 20:859–871

    Article  PubMed  CAS  Google Scholar 

  • Máthé A, Komka K, Forczig M, Szabó D, Anderlik P, Rozgonyi F (2006) The effect of different doses of cisplatin on the pharmacokinetic parameters of cefepime in mice. Lab Anim 40:296–300

    Article  PubMed  Google Scholar 

  • Pihlainen K, Ojanperä I (1998) Analytical toxicology of fluorinated inhalation anaesthetics. Forensic Sci Int 97:117–133

    Article  PubMed  CAS  Google Scholar 

  • Robbiano L, Baroni D, Carrozzino R, Mereto E, Brambilla G (2004) DNA damage and micronuclei induced in rat and human kidney cells by six chemicals carcinogenic to the rat kidney. Toxicology 204:187–195

    Article  PubMed  CAS  Google Scholar 

  • Rozgaj R, Kasuba V, Brozović G, Jazbec A (2009) Genotoxic effects of anaesthetics in operating theatre personnel evaluated by the comet assay and micronucleus test. Int J Hyg Environ Health 212:11–17

    Article  PubMed  Google Scholar 

  • Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  PubMed  CAS  Google Scholar 

  • Speit G, Hartmann A (2005) The comet assay: a sensitive genotoxicity test for the detection of DNA damage. Methods Mol Biol 291:85–95

    PubMed  CAS  Google Scholar 

  • Spracklin DK, Hankins DC, Fisher JM, Thummel KE, Kharasch ED (1997) Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J Pharmacol Exp Ther 281:400–411

    PubMed  CAS  Google Scholar 

  • Topouzova-Hristova T, Daza P, Garcia-Herdugo G, Stephanova E (2006) Volatile anaesthetic halothane causes DNA damage in A549 lung cells. Toxicol In Vitro 20:585–593

    Article  PubMed  CAS  Google Scholar 

  • Zaniboni A, Prabhu S, Audisio RA (2005) Chemotherapy and anaesthetic drugs: too little is known. Lancet Oncol 6:176–181

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The study was funded by departmental funding only. There are no conflicts of interest.

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Correspondence to Gordana Brozovic.

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Brozovic, G., Orsolic, N., Knezevic, F. et al. The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice. J Appl Genetics 52, 355–361 (2011). https://doi.org/10.1007/s13353-011-0046-0

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  • DOI: https://doi.org/10.1007/s13353-011-0046-0

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