The purpose of this study was to elucidate the molecular mechanism of action of geranylgeranylacetone, an antiulcer drug. Treatment with ethanol for 8 hr at the optimum concentration (7.5%) caused apoptotic DNA fragmentation in cultured guinea pig gastric mucosal cells. Pretreatment of cells with geranylgeranylacetone suppressed the DNA fragmentation in a dose- dependent manner. The maximum effect was achieved at 10-6 M, at which concentration the drug was previously shown to induce heat-shock proteins. The suppression required an incubation period longer than 1 hr. Pretreatment of cells with low concentrations of ethanol also prevented DNA fragmentation.
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