Department of Toxicology
The departments of Pharmacology (chaired by Prof.Dr. Martin J. Lohse), and Toxicology constitute the Institute of Pharmacology and Toxicology. The building accommodates the research laboratories and offices, a lecture hall seating 300 students, course laboratories, a seminar room, and a library for pharmacology and toxicology. Facilities for work with high levels of radioactive isotopes, a repair shop, and computer facilities for medical students are also available.
The workforce of the department of Toxicology comprises about 50 members. Four research groups are led by the University Professor Dr. Helga Stopper, the Associate Professor Dr. Wolfgang Dekant,the Associate Professor Dr. Angela Mally, and Dr. Henning Hintzsche. Postdocs and Ph.D. students with degrees in chemistry, food chemistry, biology, pharmacy, and medicine accomplish the experimental work, supported by technicians.
Main Research Interests
Our research focuses on elucidating the first-line interactions of mutagenic and carcinogenic chemicals with biological targets, with the aim of a mechanistically supported risk characterization of chemically induced cancer in humans. We investigate the kinetics and metabolism of chemicals in vitro, in cells, animals and humans, paying special attention to the metabolic activation to chemically reactive intermediates, their interaction with biological macromolecules such as DNA and protein, and their detoxification. We study genotoxicity by analyzing covalent DNA binding, induction of other types of DNA damage (see Figures) and the course of events leading to mutations. Epigenetic mechanisms include modulation of DNA methylation and histone acetylation, hormonal effects, changes in the cell cycle and disturbance of cell differentiation.
“The Comet Assay”: DNA fragments induced by a genotoxic agent migrate in an electric field out of the cell nucleus (Head) into a Tail.
“The Micronucleus Test”: Chromosome damage is indicated by the presence of a DNA-containing fragment in the cytoplasm of the bi-nucleated cell in the middle of the three cells.
A second research focus are biomarkers in both animals and humans. Biomarkers of exposure are based mainly on the analysis of metabolites in urine and on cytogenetic alterations, for example in peripheral lymphocytes and buccal mucosa cells in humans. In animal models, early molecular and cellular alterations are also investigated in the search of early biomarkers of toxicity and carcinogenicity in kidney and liver, including idiosyncratic reactions. Biomarkers of individual susceptibility are studied in connection with side effects of radiotherapy and differences in metabolism due to genetic polymorphisms or inhibition of enzymes involved in resorption, metabolism and excretion.
Alternatives to Animal Testing
A further aim is to accelerate the transition of chemical safety testing from animal-based approaches with limited predictivity for human risk to more predictive, animal-sparing solutions by developing new mechanism-based in vitro methods and assessing the confidence in risk assessment based on in vitro data.
Knowledge on the mode of toxic action is a prerequisite for biologically based extrapolation from cells in culture or laboratory animals to humans, from high dose to low dose, and from the reproducible situation of experimental systems to the heterogeneity of a human population. Efforts on dose-response relationships and mixture effects are based on experimental data but include elaborate statistical analysis as well as kinetic modeling.
The list of investigated compounds comprises a variety of chemical classes and sources. Exposure at the work place and in the environment include aromatic hydrocarbons and substituted derivatives, as well as chlorinated and fluorinated chemicals. Dietary exposure includes mycotoxins (ochratoxin A, fumonisin B1), heat-derived products (acrylamide, furan), migrants from polymers and phytoestrogens. For drugs, we focus on agents for which the probability of side effects is modulated by environmental factors, pharmacogenetic differences and/or enzyme inhibition. Compounds with estrogenic and antiestrogenic activity are used primarily in connection with the investigation of epigenetic effects. Endogenous (insulin) and unavoidable DNA-damaging agents and processes that contribute to “spontaneous” tumor formation are also of interest. Oxidative stress is considered a major factor in this respect.
Teaching and Consulting
Our staff covers all aspects of toxicology and shares the responsibility with the Pharmacology Department for teaching general and systematic pharmacology for students of medicine and biomedicine, pharmacy, dentistry, and biology. For chemistry students, a special course meets the legal requirements according to the “Gefahrstoffverordnung” to allow graduates to do business in chemical manufacture and sale. Prof. Stopper is speaker of the class “Biomedicine” of the Graduate School of the University. The working group leaders contribute to the postgraduate courses organized by the Society of Toxicology of the DGPT to register as DGPT and EUROTOX-certified Toxicologist. The institute offers advanced education for the degree of Pharmacist for Toxicology and Ecology. Editing and reviewing for scientific journals, membership in national and international scientific committees and consulting of political and governmental bodies is another part of our activities in the field. For the chemical and pharmaceutical industry, we offer both theoretical and experimental expertise for cooperations.
Activities in Committees
Prof. Dekant is a member of the Managing Board of the German Society of Pharmacology and Toxicology, Member of the European Food Safety Authority (EFSA), Member of the Scientific Committee on Health and Environmental Risks (SCHER) and a consultant of the European Union.
Prof. Dr. H. Stopper is head of the Programm Committee of the Germen Toxicological Society (GT).
Prof. Lutz is a consultant of the Federal Ministries of Environment and Health, a member of the Scientific Advisory Board of the German Drug Administration and he serves in the BAT Group of the German MAK Commission.
Prof. Dr. H. Stopper received 1996 the "Young Scientist Award" of the European Environmental Mutagen Society, 1999 the prize of the Zonta-Club for outstanding scientific research, 2001 the Bernd Tersteegen prize and 2002 the Award "Pro Meritis Scientiae et Litterarum" of the Bavarian State Ministry for Science, Research and Arts. In 2015 she received the award of the German Society for Mutation Research (Gesellschaft für Umwelt-Mutationsforschung, GUM).
Prof. Dr. A. Mally received in 2005 the Münchner Mykotoxinstipendium zur Förderung von Forschung und Fortbildung auf dem Gebiet der Mykotoxinforschung, from the Gesellschaft für Mykotoxinforschung e.V. (€ 5000,-) and in 2006 the Young Investigator Award "Toxicology", of the Deutsche Gesellschaft für Pharmakologie und Toxikologie (DGPT) (€ 2500,-)
Dr. N. Schupp received in 2007 the Fritz-Wörwag-Nachwuchs-Förder-Preis for her work on the protective effects of Vitamin B1 (€ 2500,-).
Dr. H. Hintzsche was supported from 2009 until 2011 by a stipend from the Elite Network of Bavaria. He received the Platform Competition Awards of the Bioelectromagnetics Society in 2010, the Young Scientist Award of the Microwave Applications Society India in 2011, and the Young Scientist Awards of the German Environmental Mutagen Society (Preis für junge Wissenschaftler der Gesellschaft für Umwelt-Mutationsforschung).