DNA damage and repair after exposure to sevoflurane in vivo, evaluated in Swiss albino mice by the alkaline comet assay and micronucleus test.
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.
Department of Anaesthesiology and ICU, University Hospital for Tumours, HR-10 000 Zagreb, Ilica 197, Croatia. gordana.brozovic@kzt.hr
G
G
Brozovic
N
N
Orsolic
R
R
Rozgaj
V
V
Kasuba
F
F
Knezevic
A H
AH
Knezevic
V
V
Benkovic
D
D
Lisicic
N
N
Borojevic
D
D
Dikic
D000818:Animals; D001921:Brain / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D051379:Mice; D015162:Micronucleus Tests; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D000077149:Sevoflurane
D008738:Methyl Ethers; D010975:Platelet Aggregation Inhibitors; D000077149:Sevoflurane