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Biological effects of inhaled anaesthetics halothane, sevoflurane and isoflurane on human tumour cells

Cytotoxic and antiproliferative effects of halothane, isoflurane and sevoflurane in anaesthetic doses on colon carcinoma (Caco-2), larynx carcinoma (HEp-2), pancreatic carcinoma cells (MIA PaCa-2), poorly differentiated cells from lymph node metastasis of colon carcinoma (SW-620) and normal fibroblasts were investigated. Cells were exposed to anaesthetic gas mixture consisting of O2: N2O (35:60 vol%), halothane (1.5 vol%) or isoflurane (2.0 vol%) or sevoflurane (3.0 vol%), and CO2 (5 vol%), for 2, 4 and 6 hours. Cytotoxicity of anaesthetics was analysed by validated tetrazolium dye assay MTT-test. Antiproliferative activity of halothane was measured via radioactive precursors incorporation assay. All anaesthetics expressed cytotoxic effects on treated tumour cells in time and cell line dependent manner. Growth suppression in cells exposed to halothane was enhanced in HEp-2 (69, 4%), Caco-2 (72, 5%), and SW620 cells (80, 8%), and was minimal in normal fibroblasts (90, 2%). In by halothane treated tumour cells inhibition in DNA (52, 4%, p=0, 001), and RNA (39, 2%, p=0.0006) in Caco-2 cells, as well as protein synthesis in Caco-2 cell line (19, 2%, p=0, 004), HEp-2 cells (14, 0%, p=0, 0004), and in SW620 cells (24, 48%, p=0, 007) were observed after 4 hours. A fragmentation of DNA was observed in Caco-2 and MIA PaCa-2 cells. Exposition of phosphatidylserine on outer lipid bilayer plasma membrane of by halothane treated tumour cells proofed apoptosis as mode of cell death.

Anaesthetics; inhaled; halothane; isoflurane; sevoflurane; human tumour cells; MTT; DNA synthesis; RNA synthesis; protein synthesis

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