Evaluation of DNA damage in vivo induced by combined application of cisplatin and sevoflurane.
OBJECTIVE
The influence of the combined application of cisplatin and sevoflurane on a variety of cell types of healthy mice or mice bearing Ehrlich ascites tumour has been investigated in an in vivo study.


METHODS
The alkaline comet assay method was carried out on peripheral blood leucocytes, brain, liver, kidney and tumour cells of healthy mice or mice bearing Ehrlich ascites tumour. Groups of mice were treated intraperitoneally with cisplatin, exposed to sevoflurane or by combined treatment of sevoflurane after treatment with cisplatin for 3 consecutive days.


RESULTS
The in vivo exposure to sevoflurane induced genotoxicity to all assayed cells. A strong synergistic genotoxic effect to peripheral blood leucocytes, liver and kidney cells was found in mice receiving both cisplatin and sevoflurane. In contrast, a decrease of the comet tail lengths of brain cells in the combined treatments was found as compared to cisplatin alone in both healthy (P < 0.001) and Ehrlich ascites tumour-bearing mice (P < 0.05), respectively. In addition, Ehrlich ascites tumour cells of mice treated with combined treatments showed a decrease in tail lengths (P < 0.001). These findings indicate an antagonistic effect of combined treatments.


CONCLUSIONS
Treatment of mice with cisplatin and sevoflurane induced genotoxic effect in peripheral blood leucocytes, liver, kidney, brain and Ehrlich ascites tumour cells; synergistic effect of combined treatments was expressed in all cells but brain and Ehrlich ascites tumour cells.
Brozovic
G
G
University Hospital for Tumours, Department of Anaesthesiology and ICU, Zagreb, Croatia. gordana.brozovic@kzt.hr
Orsolic
N
N
Knezevic
F
F
Horvat Knezevic
A
A
Benkovic
V
V
Vrdoljak
D V
DV
Saric
A
A
D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001921:Brain / Q000166:cytology / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000235:genetics; D002945:Cisplatin / Q000633:toxicity*; D020552:Comet Assay / Q000379:methods; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D022781:Hepatocytes / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D051379:Mice; D000077149:Sevoflurane; D018709:Statistics, Nonparametric
D018685:Anesthetics, Inhalation; D000970:Antineoplastic Agents; D008738:Methyl Ethers; D000077149:Sevoflurane; D004247:DNA; D002945:Cisplatin