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BMG research prize for "reducing and replacing animal experiments 1999" awarded in BgVV

22/2000, 28.09.2000

The State Secretary in the Federal Ministry of Health, Erwin Jordan, presented this year's research prize for the promotion of methodological work seeking to reduce and replace animal experiments to a team of scientists from the Tierärztliche Hochschule Hannover (TiHo) Hanover (Veterinary University) and the Research Centre Karlsruhe. Prof. Dr. Heinz Nau and Dr. Dr. Alfonso Lampen (Central Department for Food Toxicology of TiHo) and Dr. Martin Göttlicher (Institute for Toxicology and Genetics of the Research Centre Jülich) were presented with the prize on 28 September 2000 at the Federal Institute for Health Protection of Consumers and Veterinary Medicine in Berlin.

The three research scientists have developed a new method whereby the number of animal experiments can be reduced. These new tests can be used in the early phase of medicinal product development to identify substances which could damage the embryo during pregnancy. The research scientists use cell cultures which means that the number of later animal experiments can be reduced.

At present, medicinal products and environmental substances are mostly tested in animal experiments for their teratogenic effect. The substances concerned are administered to gestating experimental animals during a specific development period. The effects on the developing germ (embryo, foetus) are examined. The focus is on structural abnormalities in the skeleton and the organs. The creation mechanism behind these teratogenic effects is mostly unknown which means that knowledge about transferability to humans is very unreliable.

The three scientists have developed new in vitro methods in the course of their co-operation spanning several years. These are methods involving cell cultures. The goal was to identify those compounds in a substance class of similar compounds which are teratogenic. These substances are all derived from the medicinal product containing valproic acid. After treatment during pregnancy in human beings it can also lead to severe abnormalities in the embryo (above all open back, spina bifida). With these tests it is now possible to recognise embryopathic compounds without animal experiments early on in the development phase of new medicinal products.

The developed cell culture systems supply additional information. They provide insight into the molecular mechanisms of the substance effects on the organism. This should contribute to the development of new, safe medicinal products which have the desired pharmacological effects combined with far lower teratogenic potential.

This is how the scientists proceeded:

A number of structurally related substances were synthesised and their teratogenic action was characterised in mice. Here it was shown that the teratogenic effect - in contrast to the pharmacological effect - was closely linked to the structure of the substances.

These substances were then examined using the new in vitro methods. Here differentiation of F9-teratocarcinoma cells (cells corresponding to early embryonal development) was taken as the end point. A quantitative result was obtained through determining the activity of a reporter gene (for luziferase) by means of the arising luminescence. The activity of the substances in transfected F9 cells correlated significantly with teratogenic activity in vivo.

The influence of core receptors was determined in order to examine molecular mechanisms of action which control, in their capacity as transcription factors, the expression of target genes. It was shown that the activation of a specific core receptor, the so-called PPAR-d, correlates in vitro with the teratogenic effect in vivo.

The award winners can be contacted on the numbers below for any more extensive questions:
Prof. Dr. Dr. h.c. Heinz Nau Tel. 0511/856-7600
Dr. Dr. Alfonso Lampen Tel. 0511/856-7601
PD Dr. Martin Göttlicher Tel. 07247/82-4906


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