Activation of the hsp70 promoter by environmental inorganic and organic chemicals: relationships with cytotoxicity and lipophilicity

Stress proteins (heat shock proteins, HSPs) have been proposed as general m arkers of cellular aggression and their use for environmental monitoring is often suggested. The aim of this work was to study the potency of various environmentally relevant organic and inorganic chemicals to induce the expr ession of the HSP70 marker. For this purpose, we used an established HeLa c ell line-containing the chloramphenicol acetyl transferase (CAT) gene under the control of the hsp70 promoter. The screening of three metallic and 15 organic chemicals revealed differences in their capacities to induce the hs p70 promoter. The three metals tested (cadmium, zinc and mercury) were able to induce a stress response. Some organochlorine compounds (chlorophenol d erivatives, tetrachlorohydroquinone, 3,4-dichloroaniline, ethyl parathion a nd 1-chloro-2,4-dinitrobenzene) induced a response, whereas other common ha logenated pesticides or aromatic hydrocarbons (e.g. benzo(a)pyrene: 2,4-dic hlorophenoxyacetic acid, endosulfan, diuron, 4-nonylphenol) did not. The po tency to induce hsp70 was significantly correlated to the octanol-water par tition coefficient (log K-ow) of the inducing chemicals, except for 1-chlor o-2,4-dinitrobenzene and ethyl parathion. Cytotoxicity assays run in parall el to the induction measurements revealed that the three metals were effect ive at non cytotoxic doses whereas all organic compounds, except tetrachlor ohydroquinone and 1-chloro-2,4-dinitrobenzene, induced the promoter at cyto toxic doses. These results suggest that hsp70 is induced by different mecha nisms of toxicity. We propose that this model can be used in mechanistic st udies for the detection of toxic effects of certain pollutants. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.