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Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen
Author(s) -
O'Leary Geraldine,
Bacon Christopher L.,
Odumeru Oladapo,
Fagan Carl,
Fitzpatrick Therese,
Gallagher Helen C.,
Moriarty Denis C.,
Regan Ciaran M.
Publication year - 2000
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(99)00109-4
Subject(s) - enflurane , isoflurane , sevoflurane , chemistry , pharmacology , in vivo , halothane , teratology , in vitro , anesthesia , biochemistry , medicine , biology , organic chemistry , fetus , pregnancy , genetics , microbiology and biotechnology
The antiproliferative potential of the volatile anesthetics isoflurane, enflurane and sevoflurane was determined and compared to the valproate teratogen. The in vitro system employed, a G1 phase proliferative arrest endpoint in C6 glioma, has served previously to discriminate agents with known teratogenic potential in vivo. Based on estimated IC 50 values that were within twice the estimated minimum aveolar concentration value, the rank antiproliferative potency of the inhalational anesthetics employed was isoflurane=enflurane≫sevoflurane. Flow cytometric analysis of growth‐arrested cell populations failed to reveal specific accumulation in any cell cycle phase and the lack of a G1 phase‐specific effect was confirmed by the absence of a transient, time‐dependent sialylation event in synchronized cells. The antiproliferative mechanism of volatile anesthetics, and valproate, was mediated at hydrophobic binding sites, as increasing the hydration sphere of the drug‐micelle complex, using the hygroscopic qualities of the dimethylsulfoxide vehicle, completely reversed this effect. Our findings suggest inhalational anesthetics lack the specific in vitro characteristics of the valproate teratogen.