Position

Professor and Head of Centre for Toxicology

Areas of Expertise

Effects of Endocrine Disrupting Environmental Pollutants, Antitumour Drugs, Biochemistry of Carcinogenic Metal Compounds, Environmental Toxicology, Environmental Oestrogens, Cytotoxicity, Organochlorine Pollutants, Apoptosis, Novel Drug Carrier Systems, and Analysis of DNA Damage (Single Cell Electrophoresis Assay and Other Techniques).

Biography

Professor Andreas Kortenkamp studied Chemistry, Philosophy and Educational Sciences at Muenster University, Germany, where he received his first degree in 1982. In 1984 he was awarded a postgraduate fellowship from Bremen University (Germany) to undertake a project on molecular mechanisms of chromium(VI)-induced carcinogenesis. He obtained his PhD in 1989.

In 1990 he gained a postdoctoral fellowship of the European Science Foundation and moved to Queen Mary and Westfield College in London to carry out work on DNA-reactive metal compounds. In 1991 Professor Kortenkamp was appointed to a lectureship at The School of Pharmacy, University of London. He was promoted to professor in August 2007. Current work focuses on the mode of action of endocrine active chemicals and the ways in which they interact when present as mixtures.

Research Interests

Professor Andreas Kortenkamp’s research interests lie in environmental pollutants that have the potential to cause cancer. More recently, he has concentrated on endocrine active chemicals in the environment and their potential role in the rising incidences of breast cancer and testis cancer. His earlier work was on the mode of action of chromium(VI) compounds which are well recognised occupational carcinogens.

Professor Kortenkamp has specialised on exploring the effects of multi-component mixtures of endocrine active chemicals. The thrust of this work is to assess whether the effects of mixtures of chemicals can be predicted quantitatively on the basis of information about their individual potency. Recent work with endocrine active chemicals, carried out by Elisabete Silva and Nissanka Rajapkase in his research group, has shown that this is possible in reporter gene assays sensitive to estrogen-like agents. These studies have also demonstrated that significant effects can occur when each mixture component is present at concentrations that individually would not induce detectable responses.

Professor Kortenkamp has a general interest in chemicals policy and all aspects of risk assessment for environmental pollutants.

Projects

Combination effects of estrogenic chemicals in European surface waters

There is growing concern that fish in surface waters (marine and freshwater) of the European Union are exposed to natural and man-made chemicals that have the ability to mimick estrogens. These chemicals can lead to reproductive dysfunction ("endocrine disruption") in fish. They enter surface waters via effluents from sewage treatment works, industrial sources and run-off from agriculture.

A crucial aspect of identifying the causes of endocrine disruption in aquatic organisms is to analyse whether, and how, chemicals implicated as causative agents may act together when present in mixtures. The importance of considering such combination effects was highlighted in recent work with mixtures of non-estrogenic aquatic toxicants, and with estrogenic agents. These studies suggested that hazards existing in mixed exposure situations (as usually occurs) may go undetected when assessments focus exclusively on the effects of single chemicals.

Professor Kortenkamp's research group is involved in an EU-funded project, ACE (EVK1-CT-2001-00100), that addresses these issues. The project aims to improve the hazard assessment of endocrine disrupting chemicals by analysing and assessing the effects of multi-component mixtures of xenoestrogens on biological systems ranging from the subcellular level to populations of fish.

More information about the ACE project and it’s aims and achievements can be found at www.the-ace-project.info

Low-dose- and mixture-effects of endocrine active chemicals and their mode of action

Professor Kortenkamp is the coordinator of a large EU-funded project, EDEN (QLK4-CT-2002-00603). It involves 21 partner laboratories from 10 European countries. EDEN is an interdisciplinary effort designed to address knowledge gaps in the endocrine disruption field. It adopts an integrative approach to assess human and wildlife exposures, mechanisms and low-dose/mixture-evaluations.

His team is responsible for the design and stastical assessment of dose-response experiments and of mixture experiments. A second strand of work carried out in the Centre of Toxicology will analyse mechanisms involved  in the action  of endocrine disrupters. These studies employ a wide range of cell biological  and molecular biological techniques.

More detailed information about EDEN project is available at www.edenresearch.info.

CREDO - a European research cluster on endocrine disruption

The European Commission, with its 5th Framework programme for research, has supported a large number of research projects on endocrine disrupters. To facilitate an exchange of know-how, cross -fertilisation across project boundaries and other joint activities, the European Commission has set up the CREDO cluster. The cluster is coordinated by Professor Andreas Kortenkamp. Please go to www.credocluster.info if yo9u are interested in further information about cluster and its aims.

Anticancer combination chemotherapy - assessing the combiner effects of anticancer drugs in clincal use

Durable, complete remissions after treatment with single anticancer agents are rarely achieved, with toxicity and drug resistance presenting additional obstacles. To deal with these challenges, combination chemotherapy was developed and has become the norm in the treatment of many cancers today. However, the design of combination regimens is rarely based on systematic, theory-led approaches, being mostly empirical.

With this project we wish to provide leads  to the optimisation of anticancer combination therapy by assessing the predictability of joint effects of multiple anticancer drugs. This will be achieved by

• analysing whether the joint effect of mixtures of multiple anticancer drugs can be predicted from knowledge of their individual potency       

 and by

• evaluating the usefulness of various pharmacolgical concepts for the calculation of joint effects.

This project  is carried out in cooperation with Dr Mark Searcey (Department of Pharmaceutical and Biological Chemistry) and with Emeritus Professor Alexander Florence (former Dean of The School of Pharmacy).

Rajapakse N, Butterworth M, Kortenkamp A, Detection of DNA strand breaks and oxidized DNA bases at the single-cell level resulting  from exposure to estradiol and hydroxylated metabolites. Environ. Mol Mutagenesis (4): 397-404 2005

Rajapakse N, Silva E, Scholze M, Kortenkamp A, Deviation from additivity with estrogenic mixtures containing 4-nonylphenol and 4-tert-octylphenol detected in the E-SCREEN assay. Environ. Sci. Technol. 38 (23): 6343-6352 2004

Shayer R, Kinchesh P, Raffray M, Kortenkamp A, Biomonitoring of chromium (VI) deposited in pulmonary tissues: pilot studies of magnetic resonance imaging technique in a post-mortem rodent model. Biomarkers 9 (1): 32-46 2004

Peck M, Gibson RW, Kortenkamp A, Hill E, Sediments are major sinks of steroidal estrogens in two United Kingdom rivers. Environ. tox.Chem. 23 (4): 945-952 2004

Rajapakse N, Silva E, Kortenkamp A, Combining xenoestrogens at levels below individual No-observed-effect concentrations dramatically enhances steroid hormone action Environ. Health Persp. 110 (9): 917-921 2002

Silva E, Rajapakse N, Kortenkamp A, Something from "nothing" - Eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects Environ. Sci. Technol. 36 (8): 1751-1756 APR 15 2002

Payne J, Scholze M, Kortenkamp A, Mixtures of four organochlorines enhance human breast cancer cell proliferation Environ. Health Persp. 109 (4): 391-397 APR 2001

Rajapakse N, Ong D, Kortenkamp A, Defining the impact of weakly estrogenic chemicals on the action of steroidal estrogens, Toxicol. Sci. 60 (2): 296-304 APR 2001