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In the last few years plasmid-based transgenic mice which can be used for genotoxicity testing have been devised, though no such models have yet been produced for the evaluation of toxic, non-genotoxic chemical compounds. We present here a novel approach to this problem based on transgenic mice. 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 by 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. A similar, although sometimes lower, response was seen when animals treated with arsenite, cadmium or copper were re-tested with arsenite or copper. Our results show that these mice can significantly improve our understanding of the toxicity patterns of various compounds. In addition, this approach will allow a consistent reduction in the number, as well as in the suffering of animals involved in toxicity tests.

Additional information

Authors: SACCO M G ET AL, Institute of Advanced biomedical Technologies, National Research Council, Milan (IT);CHIESA G ET AL, Institute of Pharmacological Sciences, Milan (IT);CLERICI L A, JRC Ispra (IT)
Bibliographic Reference: Article: Nature Biotechnology (1997)
Record Number: 199810239 / Last updated on: 1998-03-09
Original language: en
Available languages: en
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