Induction of the human growth hormone gene placed under human hsp70 promoter control in mouse cells: a quantitative indicator of metal toxicity.
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 of 31 metals, 17 were competent for 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 positive/negative compounds also fitted well with data from genotoxicity and carcinogenesis studies on metal salts.
Fischbach
M
M
Research Laboratories Dompè S.p.A. L'Aquila, Varese, Italy.
Sabbioni
E
E
Bromley
P
P
D016475:3T3 Cells; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects*; D013006:Growth Hormone / Q000096:biosynthesis / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008670:Metals / Q000633:toxicity*; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014162:Transfection
D006360:Heat-Shock Proteins; D008670:Metals; D011993:Recombinant Fusion Proteins; D013006:Growth Hormone