Comparison of genotoxicity of sevoflurane and isoflurane in human lymphocytes studied in vivo using the comet assay

In the present paper, we report data on the possible genotoxic properties o f two inhalation anaesthetics - sevoflurane (SVF) and isoflurane (ISF) - in peripheral blood lymphocytes of patients before, during and after anaesthe sia as compared to an unexposed control group. Both anaesthetics were evalu ated for genotoxic activity using the comet assay. The exposed groups consi sted of 24 ASA grades 1-2 unpremedicated patients (aged 20-66 years, anaest hetized 115-162 min for elective lower abdominal surgery), while the contro l group consisted of 12 healthy individuals. After induction of anaesthesia (thiopenthone sodium 5-7 mg/kg, fentanyl citrate 0.1 mg and vecuronium bro mid 0.1 mg/kg), anaesthesia was maintained with inhalation of SVF 1-1.5% (n = 12) or ISF 1-1.5% (n = 12) in oxygen-air mixture. Venous blood samples w ere obtained before the induction of anaesthesia, at 60 and 120 min of anae sthesia and on the first, third and fifth days following anaesthesia. The c omet assay detects DNA damage which includes strand breaks and alkaline lab ile sites induced directly by genotoxic agents as well as DNA degradation d ue to cell death. One hundred cells from each sample were examined and grad ed as no tailed, short and long tailed nuclei. The mean comet response was not different between controls and patients before anaesthesia. However, si milar significant increases were observed in the mean comet response in blo od sampled from patients at 60 (36.5 +/- 11.2, 37.8 +/- 12.1), or 120 min ( 53.1 +/- 17.1, 50.0 +/- 12.2) of anaesthesia and on the first day (37.8 +/- 15.1, 35.2 +/- 15.7) after anaesthesia in SVF and ISF treated groups, resp ectively. Removal of the DNA damage was observed after the third day of ana esthesia and the repair was completed within 5 days. The DNA damage detecte d in lymphocytes of patients during anaesthesia with SVF or ISF showed simi lar results as demonstrated by an increased mean comet migration at 120 min of anaesthesia and the cells were able to repair the induced DNA damage co mpletely on the fifth postoperative day. (C) 2001 Elsevier Science B.V. All rights reserved.