Some metal compounds are essential for human health when consumed or inhaled in small doses; others can quickly become toxic. For more than 25 years, Prof. Dr. Andrea Hartwig has been investigating the quantities of metal compounds that have a beneficial or toxic effect on human health. As a basic researcher, the new chair of the Department of Food Chemistry and Toxicology at the Karlsruhe Institute of Technology (KIT) has managed to clarify many mechanisms of action of toxic metals, including on the molecular level. She also lends her expertise to social issues: At what level does a dose become a poison?
A healthy human diet needs to contain minerals – but only in trace amounts. Trace amounts of metals such as selenium, zinc, iron or copper are indispensable for the proper functioning of biochemical processes in the human body, for example they play a role as components of enzymes or proteins that repair DNA damage. A well-balanced diet provides the human body with optimal types and quantities of foods for maintaining cells, tissues and organs and for supporting growth and development. But what happens if we (for example in the case of excess quantities of food supplements) consume higher quantities than necessary? What happens if we ingest toxic metals such as lead, arsenic or cadmium with the food we eat? “Which molecular mechanisms lead to metal poisoning?” is the question posed by Prof. Dr. Andrea Hartwig from the Department of Food Chemistry and Toxicology at the Karlsruhe Institute of Technology (KIT). “And what concentrations of essential trace minerals are toxic rather than beneficial for human health?”
These are the questions that Prof. Hartwig has been trying to answer ever since she did her doctorate. The chemist and toxicologist was appointed professor at the Karlsruhe Institute of Technology in 2010. Born in Langenhagen close to Hanover, Germany in 1958, Andrea Hartwig studied chemistry at the University of Bremen and received her doctoral degree in 1987 for her work on the mutagenicity and co-mutagenicity of nickel and cadmium compounds. While she was doing her doctorate, she spent three months at the Institute of Environmental Medicine in the state of New York (USA). She was a postdoctoral research fellow before becoming scientific assistant at the University of Bremen from 1988 to 1998. In 1996, she habilitated in the field of biochemistry. From 1998 to 2004, Hartwig was professor of food chemistry at the University of Karlsruhe, and in 2004 she was appointed professor of food chemistry at the Technical University of Berlin. Hartwig returned to Karlsruhe in autumn 2010.One of her major research projects focuses on the impact of essential trace elements such as toxic metals on genetic stability. Trace minerals such as zinc and iron are found within proteins that repair errors in the DNA sequence or breakages in the molecular DNA structure. Using biochemistry and molecular biology methods, Hartwig and her team have shown for example that toxic metals interfere with the DNA repair mechanisms by interacting with essential trace minerals contained in the repair proteins. “Since they have similar chemical properties, toxic metals displace their essential relatives from the protein molecules and inhibit their correct function,” said Hartwig. Hartwig and her team have already been able to elucidate this mode of action of cadmium, an extremely toxic heavy metal that is toxic even in very low concentrations. Cadmium is found in the environment and we therefore take up small quantities of cadmium with the food we eat.
What makes metals so dangerous for cells is their electrochemical properties; in suitable environments, transition metals easily take up or give off electrons. Copper is an excellent example of a metal with electrochemical properties that turn trace minerals into a double-edged sword. Copper is essential for many cellular enzymes (for example respiratory chain enzymes where its electrochemical properties play an important role). Copper does not normally appear in its free form in cells, where it is always bound to proteins. However, if we take up too great a concentration of copper, the cells are no longer able to bind all copper molecules. In this case, the free copper ions catalyse so-called redox reactions inside the cells, which causes electrons to be transferred. This leads to the generation of reactive oxygen species that can damage DNA and proteins. “This example clearly shows that the correct concentration is a key issue as far as trace minerals are concerned,” said Hartwig.Hartwig's investigations also cover the mechanisms that regulate the homoeostasis of trace minerals in cells and the concentrations at which trace elements can become toxic. She is also very interested in a risk assessment of social relevance. She has been chairperson of the Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area of the German Research Foundation (MAK Commission) since 2007 and is also a European Food Safety Authority (EFSA) expert. “The goal of these institutions is to set up scientifically founded limits for the exposure of humans to potentially toxic substances in the workplace and in food,” said Hartwig. What is the greatest quantity of trace elements or toxic metals humans can be exposed to before biological disorders occur?
Hartwig’s return to Karlsruhe has brought her back into an area with a broad and diversified research infrastructure. “With the numerous renowned institutions such as the Max Rubner Institute and the Karlsruhe Research Centre, Karlsruhe offers excellent possibilities for interdisciplinary research,” said Hartwig. One example of her many collaborations with Karlsruhe research groups is a project in which her team is working with colleagues from the Karlsruhe Research Centre to investigate the toxicity of metal-containing nanoparticles. How do the toxic effects of metal-containing ultra fine dust particles differ from those of micrometer-size metal particles? How does the bioavailability in the cells change? “In principle, my research always focuses on the assessment of risks and benefits,” said Hartwig. Humans have changed the environment in which we live and are thus exposed to numerous double-edged swords. So, the dose does indeed become the poison.
Prof. Dr. Andrea HartwigInstitute of Applied BiosciencesDepartment of Food Chemistry and ToxicologyAdenauerring 20 76131 KarlsruheTel.: +49 721 608 47645Fax: +49 721 608 47255E-mail: andrea.hartwig(at)kit.edu