Skip to main content
Log in

DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test

  • Original Article
  • Published:
Journal of Applied Genetics Aims and scope Submit manuscript

Abstract

The relationship between DNA damage and repair of peripheral blood leukocytes, liver, kidney and brain cells was investigated in Swiss albino mice (Mus musculus L.) after exposure to sevoflurane (2.4 vol% for 2 h daily, for 3 days). Genetic damage of mouse cells was investigated by the comet assay and micronucleus test. To perform the comet assay, mice were divided into a control group and 4 groups of exposed mice sacrificed on day 3 of the experiment, at 0, 2, 6 or 24 h after the last exposure to sevoflurane. Mean tail length (TL), tail moment (TM), and tail intensity (TI) values were significantly higher in exposed mice (all examined organs) than in the control group. Significant DNA damage immediately after exposure to sevoflurane was observed in leukocytes. Damage induction in the liver, kidney, and brain occurred 6 h later than in leukocytes, as expected according to the toxicokinetics of the drug, where blood is the first compartment to absorb sevoflurane. However, none of the tested tissues revealed signs of repair until 24 h after the exposure. To distinguish the unrepaired genome damage in vivo, the micronucleus test was applied. Number of micronuclei in reticulocytes showed a statistically significant increase, as compared with the control group at all observed times after the treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bienengraeber MW, Weihrauch D, Kersten JR, Pagel PS, Warltier DC, 2005. Cardioprotection by volatile anesthetics.Vascul Pharmacol 42: 243–252.

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Byhahn C, Heller K, Lischke V, Westphal K, 2001. Surgeon’s occupational exposure to nitrous oxide and sevoflurane during pediatric surgery. World J Surg 25: 1109–1112.

    Article  CAS  PubMed  Google Scholar 

  • Dusinska M, Collins AR, 2008. The comet assay in human biomonitoring: gene-environment interactions. Mutagenesis 23: 191–205.

    Article  CAS  PubMed  Google Scholar 

  • Halliwell B, Cross CE, 1994. Oxygen-derived species: their relation to human disease and environmental stress. Environ Health Perspect 102, Supplement 10: 5–12.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi M, Hashimoto S, Sakamoto Y, Hamada C, Sofuni T, Yoshimura I, 1994. Statistical analysis of data in mutagenicity assays: rodent micronucleus assay. Environ Health Perspect 102, Supplement 1: 49–52.

    PubMed  Google Scholar 

  • Heddle JA, Cimino MC, Hayashi M, Romagna F, Shelby MD, Tucker JD, et al. 1991. Micronuclei as an index of cytogenetic damage: past, present, and future. Environ Mol Mutagen 18: 277–291.

    Article  CAS  PubMed  Google Scholar 

  • Hobbhahn J, Wiesner G, Taeger K, 1998. Occupational exposure and environmental pollution: the roleofinhalation anesthetics with special consideration of sevoflurane. Anaesthesist 47: 77–86.

    Article  Google Scholar 

  • Holden HE, Majeska JB, Studwell D, 1997. A direct comparison of mouse and rat bone marrow and blood as target tissues in the micronucleus assay. Mutat Res 391: 87–89.

    CAS  PubMed  Google Scholar 

  • Jagetia GC, Nayak V, 2000. Effect of doxorubicin on cell survival and micronuclei formation in HeLa cells exposed to different doses of gamma-radiation. Strahlenther Onkol 176: 422–428.

    Article  CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Karabiyik L, Sardaş S, Polat U, Kocaba SNA, Karakaya AE, 2001. Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using the comet assay. Mutat Res 492: 99–107.

    CAS  PubMed  Google Scholar 

  • Keaney A, Diviney D, Harte S, Lyons B, 2004. Postoperative behavioral changes following anesthesia with sevoflurane. Paediatr Anaesth 14: 866–870.

    Article  PubMed  Google Scholar 

  • Kharasch ED, 1995. Biotransformation of sevoflurane. Anesth Analg 81, Supplement 6: 27–38.

    Article  Google Scholar 

  • Laurent C, Voisin P, Pouget JP, 2006. DNA damage in cultured skin microvascular endothelial cells exposed to gamma rays and treated by the combination pentoxifylline and alpha-tocopherol. Int J Radiat Biol 82: 309–321.

    Article  PubMed  Google Scholar 

  • Meyer RR, Münster P, Werner C, Brambrink AM, 2007. Isoflurane is associated with a similar incidence of emergence agitation/delirium as sevoflurane in young children — a randomized controlled study. Paediatr Anaesth 17: 56–60.

    Article  PubMed  Google Scholar 

  • Morgan WF, 2003. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro. Radiat Res 159: 567–580.

    Article  CAS  PubMed  Google Scholar 

  • Morgan WF, 2003. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiat Res 159: 581–596.

    Article  CAS  PubMed  Google Scholar 

  • Nishiyama T, Fujimoto T, Hanaoka K, 2004. Comparison of liver function after hepatectomy in cirrhotic patients between sevoflurane and isoflurane in anesthesia with nitrous oxide and epidural block. Anesth Analg 98: 990–993.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  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 

  • Sardaş S, Aygün N, Gamli M, Unal Y, Unal N, Berk N, Karakaya AE, 1998. 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 418: 93–100.

    PubMed  Google Scholar 

  • Sasaki YF, Nishidate E, Izumiyama F, Matsusaka N, Tsuda S, 1997. Simple detection of chemical mutagens by the alkaline single-cell gel electrophoresis (comet) assay in multiple mouse organs (liver, lung, spleen, kidney and bone marrow). Mutat Res 391: 215–231.

    CAS  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  CAS  PubMed  Google Scholar 

  • Szyfter K, Szulc R, Mikstacki A, Stachecki I, Rydzanicz M, Jałoszyński P, 2004. Genotoxicity of inhalation anaesthetics: DNA lesions generated by sevoflurane in vitro and in vivo. J Appl Genet 45: 369–374.

    PubMed  Google Scholar 

  • Wiesner G, Schiewe-Langgartner F, Lindner R, Gruber M, 2008. Increased formation of sister chromatid exchanges, but not of micronuclei, in anaesthetists exposed to low levels of sevoflurane. Anaesthesia 63: 861–864.

    Article  CAS  PubMed  Google Scholar 

  • Wong CH, Liu TZ, Chye SM, Lu FJ, Liu YC, Lin ZC, Chen CH, 2006. Sevoflurane-induced oxidative stress and cellular injury in human peripheral polymorphonuclear neutrophils Food Chem Toxicol 44: 1399–1407.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G. Brozovic.

Additional information

The study was carried out at the Department of Animal Physiology, Faculty of Science, University of Zagreb

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brozovic, G., Orsolic, N., Rozgaj, R. et al. DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test. J Appl Genet 51, 79–86 (2010). https://doi.org/10.1007/BF03195714

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03195714

Keywords

Navigation