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Induction of the human growth hormone gene placed under human hsp70 promoter control in mouse cells: A quantitative indicator of metal toxicity
Authors:Michel Fischbach  Enrico Sabbioni  Peter Bromley
Institution:(1) Research Laboratories Dompè S.p.A. L'Aquila, Ispra, (Varese), Italy;(2) Joint Research Centre-Ispra Site, Environment Institute, Life Sciences Unit, T.P. 460, Commission of the European Communities, I-21020 Ispra, (Varese), Italy;(3) Département de Génétique et Microbiologie, C.M.U., Geneva, Switzerland
Abstract:An in vitro test method for general metal toxicity screening was designed, based on the cellular response to stress. The expression of a transfected human growth hormone gene sequence driven by the human heat-shock protein 70 promoter in NIH/3T3 cells was used as marker of noxious contact with metal compounds. Out of a series of31 metals, 17 were competentfor inducing this stress response system. According to the effective concentration and to the intensity of the response, three different clusters of positive compounds emerged and were ranked as strong, intermediate strength and weak inducers. These results correlated well with data from other in vivo and in vitro metal toxicity studies, including LD50 in mice. Apparently the positivelnegative compounds also fitted well with data from genotoxicity and carcinogenesis studies on metal salts.Abbreviations hGH human growth hormone - hsp70 70 kDa heat-shock protein
Keywords:hsp70 promoter  human growth hormone  in vitro toxicity test  metals  reporter gene
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