A transgenic mouse model for the detection of cellular stress induced by toxic inorganic compounds.
Transgenic mice for genotoxicity testing have been developed, although no such models have been produced for the evaluation of toxic, nongenotoxic chemical compounds. We have developed a transgenic mouse model for the analysis of toxic inorganic compounds. We engineered a mouse lineage with the human growth hormone (hGH) gene under the control of the human hsp70 promoter, in which a plasma-detectable hGH response can be elicited by exposure to heat shock. In primary cell cultures from these mice, hGH release was observed following treatment with several toxic inorganics. Transgenic mice injected intraperitoneally with sodium arsenite, cadmium chloride, copper sulphate, or methylmercurium chloride showed significant hGH levels in plasma.
Sacco
M G
MG
Institute of Advanced Biomedical Technologies, National Research Council, Milan, Italy. sacco@itba.mi.cnr.it
Zecca
L
L
Bagnasco
L
L
Chiesa
G
G
Parolini
C
C
Bromley
P
P
Catò
E M
EM
Roncucci
R
R
Clerici
L A
LA
Vezzoni
P
P
D000818:Animals; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity; D019256:Cadmium Chloride / Q000008:administration & dosage / Q000633:toxicity; D002478:Cells, Cultured / Q000187:drug effects; D019327:Copper Sulfate / Q000008:administration & dosage / Q000633:toxicity; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018840:HSP70 Heat-Shock Proteins / Q000097:blood / Q000235:genetics*; D019382:Human Growth Hormone / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D006801:Humans; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity; D051379:Mice; D008822:Mice, Transgenic; D008957:Models, Genetic; D009152:Mutagenicity Tests; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity; D019076:Transgenes; D015262:Xenobiotics / Q000633:toxicity*
D018053:Arsenites; D018840:HSP70 Heat-Shock Proteins; D008767:Methylmercury Compounds; D017670:Sodium Compounds; D015262:Xenobiotics; D019382:Human Growth Hormone; C017947:sodium arsenite; D019256:Cadmium Chloride; D019327:Copper Sulfate; C004925:methylmercuric chloride