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 markers 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 expression of the HSP70 marker. For this purpose, we used an established HeLa cell 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 hsp70 promoter. The three metals tested (cadmium, zinc and mercury) were able to induce a stress response. Some organochlorine compounds (chlorophenol derivatives, tetrachlorohydroquinone, 3, 4-dichloroaniline, ethyl parathion and 1-chloro-2,4-dinitrobenzene) induced a response, whereas other common halogenated pesticides or aromatic hydrocarbons (e.g. benzo(a)pyrene, 2, 4-dichlorophenoxyacetic acid, endosulfan, diuron, 4-nonylphenol) did not. The potency to induce hsp70 was significantly correlated to the octanol-water partition coefficient (log K(ow)) of the inducing chemicals, except for 1-chloro-2,4-dinitrobenzene and ethyl parathion. Cytotoxicity assays run in parallel to the induction measurements revealed that the three metals were effective at non cytotoxic doses whereas all organic compounds, except tetrachlorohydroquinone and 1-chloro-2,4-dinitrobenzene, induced the promoter at cytotoxic doses. These results suggest that hsp70 is induced by different mechanisms of toxicity. We propose that this model can be used in mechanistic studies for the detection of toxic effects of certain pollutants.
Aït-Aïssa
S
S
Unité d'Evaluation des Risques Ecotoxicologiques, Institut National de l'Environnement Industriel et des Risques, BP2, 60550, Verneuil-en-Halatte, France. selim.ait-aissa@ineris.fr
Porcher
J
J
Arrigo
A
A
Lambré
C
C
D002104:Cadmium / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics*; D006367:HeLa Cells; D006358:Hot Temperature; D006801:Humans; D008670:Metals / Q000633:toxicity; D010416:Pentachlorophenol / Q000633:toxicity; D011401:Promoter Regions, Genetic; D012995:Solubility
D004785:Environmental Pollutants; D018840:HSP70 Heat-Shock Proteins; D008670:Metals; D002104:Cadmium; D010416:Pentachlorophenol