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Genetic barcode to unmask environmental toxins

In their early developmental stages, living organisms are very sensitive to exposure to chemicals. However, little information is available about whether chemical substances have a toxic effect on the developing organism and if so, in what doses. Scientists at the KIT Institute of Toxicology and Genetics (ITG) have developed a model system with fish embryos to specifically identify the effects of environmental toxins at a very early point.

The KIT scientists exposed zebrafish, Danio rerio, embryos to a range of common pollutants, including dioxin, DDT, cadmium and mercury and subsequently analysed the genetic reaction. Exposure to these pollutants activates several hundred genes in the organism, thereby leading to changes in gene-expression profiles that can be read like a genetic barcode. Using this method, the developmental biologists were able to effectively deduce the chemical to which the fish had been exposed.

“It was impressive to see how specific the genetic responses were, enabling us to identify 14 of 15 environmental toxins tested,” said the director of the ITG, Professor Uwe Strähle. The effects were already visible at concentrations that did not lead to external changes in the embryos. The method is therefore more sensitive than the currently used biomonitoring tests in which morphological alterations serve as the indicator of toxic effects.
Defective development: in this fish embryo, environmental toxins have caused the fish, which usually has a straight body, to become deformed. (Photo: Karlsruhe Research Centre)
Defective development: in this fish embryo, environmental toxins have caused the fish, which usually has a straight body, to become deformed. (Photo: Karlsruhe Research Centre)

Zebrafish embryos as a manageable vertebrate model

“In future, the system might be used to evaluate the toxicity of new pharmaceutical products and assess their potential danger as early as possible during the development process,” said Strähle. Another potential use of this technique involves the toxicological testing of chemicals that are already used by the pharmaceutical and chemical industries. The new EU REACH legislation (Registration, Evaluation and Authorisation of Chemicals), which came into effect on 1st June 2007, requires all chemical substances in use in the EU with an annual production or import quantity of at least one tonne to be tested for their effect on health and environment and be registered. A specific approval procedure is required for approximately 2,500 to 3,000 particularly dangerous chemicals, for example those with a carcinogenic effect and those that lead to a reduction in fertility.

“Zebrafish embryos are easy to handle and represent an ethically justifiable vertebrate model that can be used to deal with the tens of thousands of risk assessments that are required by REACH,” said Uwe Strähle. The model will help cope with the high demand from regulators and industry for reliable methods required to evaluate the developmental toxicity of pharmaceutical products and also has the medium-term potential for automation and hence be suitable for the rapid testing of large numbers of chemicals.

Source: Karlsruhe Institute of Technology, rl - 25.03.2008
Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/genetic-barcode-to-unmask-environmental-toxins