title: The in vivo genotoxicity of cisplatin, isoflurane and halothane evaluated by alkaline comet assay in Swiss albino mice.
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.
authors.affiliation: Department of Anaesthesiology, Reanimatology and Intensive Care Medicine, University Hospital Sv. Duh, Sv. Duh 64, Zagreb, Croatia. gbrozovic@kbsd.hr
authors.forename: Gordana
authors.initials: G
authors.lastname: Brozovic
authors.forename: Nada
authors.initials: N
authors.lastname: Orsolic
authors.forename: Fabijan
authors.initials: F
authors.lastname: Knezevic
authors.forename: Anica
authors.initials: A
authors.lastname: Horvat Knezevic
authors.forename: Vesna
authors.initials: V
authors.lastname: Benkovic
authors.forename: Katarina
authors.initials: K
authors.lastname: Sakic
authors.forename: Nikola
authors.initials: N
authors.lastname: Borojevic
authors.forename: Domagoj
authors.initials: D
authors.lastname: Dikic
mesh_terms: D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D020552:Comet Assay / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects*; D006221:Halothane / Q000008:administration & dosage / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects; D007530:Isoflurane / Q000008:administration & dosage / Q000633:toxicity*; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D009153:Mutagens / Q000633:toxicity
chemical_list: D018685:Anesthetics, Inhalation; D009153:Mutagens; D007530:Isoflurane; D002945:Cisplatin; D006221:Halothane