HEAT-SHOCK RESPONSE AND CYTOTOXICITY IN C6 RAT GLIOMA-CELLS - STRUCTURE-ACTIVITY RELATIONSHIP OF DIFFERENT ALCOHOLS

In C6 rat glioma cells, the n-alcohols methanol, ethanol, propanol, an d butanol and the aromatic alcohol phenol all induce heat shock protei ns (HSPs) of high molecular mass (68, 70, 90, and 110 kDa) when applie d for 1 hr. The lowest alcohol concentrations that induce HSP synthesi s cause about 20% cell death, as determined by neutral red assay. HSP induction thus occurs at alcohol concentrations close to the highest t olerable dose. The cytotoxicity and the potential of alcohols to induc e the synthesis of HSPs increase with chain length and are correlated with the lipophilicity of the alcohols. A clear structure-activity rel ationship is observed for both parameters. A calculation of the putati ve membrane concentrations of these alcohols reveals that cytotoxic ef fects (50% cell death) occur at nearly the same membrane concentration (approximately 0.2 M). This also holds true for the lowest HSP 68-ind ucing alcohol concentrations, but at a lower concentration (approximat ely 0.12 M). The activities of major proteinases are affected by both heat shock and alcohols. The effects of alcohols also depend on the li pophilicity of the alcohols. Effective concentrations again are close to the highest tolerable dose. The stress reactions measured in terms of significant changes in HSP synthesis and proteinase activity provid e information about the mechanisms by which toxic agents act on the ce ll.