Antiproliferative actions of inhalational anesthetics: comparisons to the valproate teratogen

The antiproliferative potential of the volatile anesthetics isoflurane, enf lurane and sevoflurane was determined and compared to the valproate teratog en. The in vitro system employ ed. a G1 phase proliferative arrest endpoint in C6 glioma, has served previously to discriminate agents with known tera togenic potential in vivo. Based on estimated IC50 values that were within twice the estimated minimum aveolar concentration value, the rank antiproli ferative 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 an tiproliferative mechanism of volatile anesthetics, and valproate, was media ted at hydrophobic binding sites, as increasing the hydration sphere of the drug-micelle complex, using the hygroscopic qualities of the dimethylsulfo xide vehicle, completely reversed this effect. Our findings suggest inhalat ional anesthetics lack the specific in vitro characteristics of the valproa te teratogen. (C) 2000 ISDN. Published by Elsevier Science Ltd. All rights reserved.