EUROTOX Speciality Section Carcinogenesis „Diet and Cancer“
held in Dortmund/Germany, May 16, 2003
1st International Conference "Molecular Research in Environmental Medicine"
Düsseldorf, March 18 - 20, 2004, Germany
12th EUROTOX Training and Discussion Session "Protective Agents in the Diet"
held in Dortmund/Germany, May 16, 2003
Food safety is a major public and scientific concern. Food toxicology investigates the impact of natural and synthetic compounds present in food on human health, taking into account dangerous effects such as carcinogenicity, allergy, immunotoxicity and neurotoxicity on the one side and the potential for the prevention of disease on the other side. It is the aim of the European Graduate College ”Molecular mechanisms in food toxicology” to contribute to the understanding at a molecular level of pathways by which food compounds exert their toxic or preventive effects. While there is a focus on molecular biological techniques to study signal transduction, gene expression and cell cycle control in most of the 10 projects, electrophysiological and analytical methods as well as neurobehavioral testing are also applied. The models used range from cell culture systems to perfused organs and intact animals. Thesis topics are divided into two sections: Section A concentrates on genotoxic and endocrine mechanisms in food toxicology while in section B the focus is on the protective effects of antioxidative food constituents. The expected research results can contribute to the setting of health-based standards and to the elaboration of preventive strategies for human health.
Students with a degree in either natural science or medicine can participate in the college. They are trained to conduct high-quality, specialized research resulting in the completion of a doctoral thesis. A German and a Dutch supervisor jointly take care of each research project. Complementary techniques from their laboratories are provided to support progress of the thesis work. The students work in both laboratories and thus have the opportunity to practise the scientific and social requirements of cooperative research. The accompanying educational programme covers a broad spectrum of toxicology, exceeding the highly specialized area of food toxicology in which the students conduct their research, teaching theoretical knowledge in all the central areas of toxicology and making students familiar with subjects of applied toxicology by involving teachers from regulatory agencies and industry. The curriculum is adapted to the requirement of national boards registering qualified toxicologists. We expect that the students when leaving the Graduate College will find jobs in a wide variety of toxicologically oriented workplaces in academia, industry and administration.
.
German
co-ordinator
Prof.Dr.Regine
Kahl
Institute for Toxicology, Heinrich Heine University Düsseldorf
Postfach 10 10 07, D-40001 Düsseldorf
Phone +49/211-81 13013, Fax +49/211-8113013
e-mail kahl@uni-duesseldorf.de
Dutch co-ordinator
Prof.Dr.J.Kleinjans
Department of Health Risk Analysis and Toxicology, University of
Maastricht
P.O.Box 616, 6200 MD Maastricht
Phone +31/43-3881097, Fax +31/43-3670924
e-mail j.kleinjans@grat.unimaas.nl
Research Institute for Environmental Medicine at
the Heinrich Heine University Düsseldorf
Auf´m
Hennekamp 52, D-40225 Düsseldorf
Phone +49/211-3389
204, Fax +49/211-3190910
e-mail josef.abel@uni-duesseldorf.de
Prof.Dr.Dr.Hermann Bolt
Institute for Occupational
Physiology at the University Dortmund
Ardeystr.67, 44139
Dortmund
Phone +49/231-1084 348, Fax +49/231-1084 403
e-mail bolt@arb-phys.uni-dortmund.de
Prof.Dr.Paul Borm
Research Institute
for Environmental Medicine at the Heinrich Heine University
Düsseldorf
Auf´m Hennekamp 52,
D-40225 Düsseldorf
Phone +49/211-3389 269,
Fax +49/211-3389 331
e-mail paul.borm@uni-duesseldorf.de
Prof.Dr.Dr.Gisela Degen
Institute for Occupational
Physiology at the University Dortmund
Ardeystr.67, 44139
Dortmund
Phone+49/231-1084 351, Fax +49/231-1084 403
e-mail degen@arb-phys.uni-dortmund.de
Prof.Dr.Ernst Gleichmann
Research Institute
for Environmental Medicine at the Heinrich Heine University
Düsseldorf
Auf´m Hennekamp 52,
D-40225 Düsseldorf
Phone +49/211-3389 244,
Fax +49/211-3190910
e-mail
ernst.gleichmann@uni-duesseldorf.de
Prof.Dr.Regine Kahl
Institute for Toxicology,
Heinrich Heine University Düsseldorf
Universitätsstr.1, D-40225
Düsseldorf
Phone +49/211-81 13013,
Fax +49/211-81 13013
e-mail kahl@uni-duesseldorf.de
Prof. Dr. Helmut Sies
Institute for
Physiological Chemistry I, Heinrich Heine University Düsseldorf
Postfach 10 10
07, D-40001 Düsseldorf
Phone +49/211-81 12707,
Fax +49/211-81 13029
e-mail: helmut.sies@uni-duesseldorf.de
Priv. Doz. Dr. Wilhelm Stahl
Institute for
Physiological Chemistry I, Heinrich Heine University Düsseldorf
Postfach 10 10
07, D-40001 Düsseldorf
Phone +49/211-81 12711,
Fax +49/211-81 13029
e-mail: wilhelm.stahl@uni-duesseldorf.de
Prof.Dr.Herbert Wiegand
Research Institute
for Environmental Medicine at the Heinrich Heine University
Düsseldorf
Auf´m Hennekamp 52,
D-40225 Düsseldorf
Phone +49/211-3389 325,
Fax +49/211-3389 331
e-mail wiegand@uni-duesseldorf.de
Prof.Dr.Gerhard Winneke
Research Institute
for Environmental Medicine at the Heinrich Heine University
Düsseldorf
Auf´m Hennekamp 52,
D-40225 Düsseldorf
Phone +49/211-3389 325,
Fax +49/211-3389 ???
e-mail gerhard.winneke@uni-duesseldorf.de
Prof.Dr.Frank Wunderlich
Department for Molecular
Parasitology, Heinrich Heine University
Universitätsstr.1, D-40225
Düsseldorf
Phone +49/211-81 13401,
Fax +49/211-81 14734
e-mail frank.wunderlich@uni-duesseldorf.de
Participants in The Netherlands
Dr.J.M.M.J.G.Aarts
Department of
Toxicology, University of Wageningen
Tuinlaan 5, 6703 HE
Wageningen
Phone +31/ 317 4 84936,
Fax +31/ 317 4 84931
e-mail: jac.aarts@Algemeen.TOX.WAU.nl
Dr.Gerrit M. Alink
Department of Toxicology,
University of Wageningen
Tuinlaan 5, 6703 HE
Wageningen
Phone +31/ 317-484294, Fax
+31/
e-mail gerrit.alink@Algemeen.TOX.WAU.nl
Prof. Dr.Aalt Bast
Department of Pharmacology
and Toxicology, University of Maastricht
Postbus 616, NL-6200 MD
Maastricht
Phone: +31/43-3881418,
Fax: +31/43-3884149
e-mail A.Bast@farmaco.unimaas.nl
Prof.Dr.Johanna Fink-Gremmels
Department of
Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine,
University of Utrecht
Yalelaan 16, NL-3508 TD
Utrecht
Phone +31/30-253 5453, Fax, +31/30-253 4125
e-mail j.fink@vfft.vet.uu.nl
Prof.Dr.Jos Kleinjans
Department of Health Risk
Analysis and Toxicology, University of Maastricht
P.O.Box 616, 6200 MD
Maastricht
Phone +31/43-3881097, Fax
+31/43-3670924
e-mail j.kleinjans@grat.unimaas.nl
Dr.Henk van Loveren
Department of
Immunobiology and Hematology, RIVM,
Postbus 1, NL-3720 BA
Bilthoven
Phone: +31/30-274 2476, Fax: +31/30 274 4437
e-mail h.van.loveren@rivm.nl
Prof.Dr.I.M.C.M.Rietjens
Department of Toxicology,
University of Wageningen
Tuinlaan 5, NL-6703 HE
Wageningen
Phone +31/317 483723, Fax
+31/317 484931
e-mail ivonne.rietjens@p450.bc.WAU.nl
Dr.Hans Temmink
Department of Toxicology,
University of Wageningen
Tuinlaan 5, NL-6703 HE
Wageningen
Phone +31/317-482656, Fax
+31/317-484931
e-mail hans.temmink@Algemeen.TOX.WAU.nl
6. Project description: Outline of the aims of the proposal,
methods and workplan
Thesis topics and supervisors
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Influence of dietary factors like poly-unsaturated fatty acids and phytochemicals on colon cancer development: roles of PGHS-2 and PPARs |
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| A2
Functional role of cytoskeletal proteins for chromosomal toxicity of phytoestrogens |
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| A3
Induction of DNA damage in human cells by ochratoxin A and other mycotoxins |
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| A4
Interactions of dietary iodine deficiency with neonatal PCBs on thyroid function and brain development in rats |
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| A5
Rapid non-genomic actions of testosterone: Intracellular signalling mechanisms and isolation of the plasma membrane receptor of testosterone |
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| B1 Pulmonary inflammation and systemic effects due to ambient particulates |
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| B2
Role of dietary flavonoids in the adaptation of antioxidant enzymes to prooxidants and pro- inflammatory mediators |
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| B3
Cooperative interactions of antioxidant micronutrients |
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| B4
Immunomodulation and altered gene expression induced by oral uptake of nickel (Ni) and zinc (Zn), respectively |
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| B5
Purinergic receptors of human macrophages: Influence of polychlorinated biphenyls and antioxidants on intracellular signal transduction and redox systems |
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A1. Influence of dietary factors like poly-unsaturated
fatty acids and phytochemicals on colon cancer development: roles of PGHS-2 and
PPARs
Abel
(Düsseldorf) / Alink (Wageningen)
Colon cancer is a major cause of death in Western countries.
This project studies mechanisms by which dietary factors can initiate and
promote colon cancer development. Two lines will be followed: 1. Omega--3
polyunsaturated fatty acids (PUFAs) – assumed to be inhibitory to tumour
development - and omega-6 PUFAs – assumed to promote tumour development - will
be compared with respect to their influence on cell proliferation and apoptosis
as well as on hydroxyl radical production and lipid peroxidation, taking into
account the role of dietary iron. 2. The enzyme prostaglandin H synthase-2
(PGHS-2) is involved in colon intestinal cell proliferation, differentiation and
apoptosis. The effects of carcinogenic dietary heterocyclic amines on PGHS-2
expression and its consequences as well as the modulation of PGHS-2 expression
by PUFAs and cancer-preventive phytochemicals will be investigated. The signal
transduction mechanisms involved in PGHS-2 expression, e.g. the role of the
transcription factor PPARg,
will be clarified.
Added value of cooperation: Both
laboratories already have PhD students working on the subject ”Prostaglandin H
synthase-2 in relation to cancer development”. The methods used are largely
complementary. The laboratory in Wageningen has expertise in animal experimental
models for colon cancer development and in cell culture systems used to
investigate gap junctional intercellular communication. The laboratory in
Düsseldorf is specialised in the cultivation of primary cells, transfection
experiments and molecular biological techniques like PCR, EMSA, and Western
blotting.
A2. Functional role of cytoskeletal proteins for
chromosomal toxicity of phytoestrogens
Bolt (Dortmund)
/ Kleinjans (Maastricht)
Phytoestrogens are natural constituents of human food. Their
“endocrine disrupting” properties are a matter of major research programmes. The
present project aims at elucidating mechanisms of interaction of phytoestrogens
and their metabolites with cytoskeletal proteins as the key macromolecules of
which interaction with foreign chemicals leads to chromo-somal genotoxic damage.
It is supposed that for such interac-tions thresholds may be defined which would
allow definitions of No-Observed-Adverse-Effect-Levels (NOAEL). This is
fundamental for setting health-based standards (e.g., ADI). Whereas in the past
the research in this field had been centered on defining major interactions of
estrogens and their metabolites with microtubular proteins, the present project
will use functional tests of tubulin-motor protein interaction to describe the
dose-response patterns of phytoestrogens and phytoestrogen metabolites, in
relation to their chromosomal genotoxicity.
Added
value of cooperation: Assisted by seed funding from CEFIC/LRI, the group in
Dortmund, in cooperation with IMB, Jena, has adopted methods to study the
function of cytoskeletal proteins and of influences of foreign compounds
thereon. The issue is of considerable regulatory impact, as it will probably
allow to define a subgroup of genotoxic compounds to which threshold levels may
be assigned. The group in Maastricht has a long-standing expertise in methods of
quantitative risk assessment. The combination of both will allow to develop new
aspects for the regulatory risk assessment of genotoxic food
constituents.
A3. Induction of DNA damage in human cells by ochratoxin
A and other mycotoxins
Degen (Dortmund)
/ Fink-Gremmels (Utrecht)
The mycotoxin ochratoxin A (OTA) is a widespread contaminant
in human and animal food. In humans, an exposure to high dietary levels of OTA
has been linked with chronic renal disease and with a higher incidence of
urinary tract tumors. A genotoxic potential of OTA has been demonstrated in
vitro and in vivo, but there is some controversy as to whether its action is
direct or indirect. The project aims at identifying the nature of the genotoxic
damage. UDS responses in human urothelial cell cultures, micronucleus
induction, single cell "COMET" assay and the functional interaction of OTA
with cytoskeletal proteins will be investigated. The most sensitive endpoint for
damage induced by OTA will be characterized, and it will be assessed whether
threshold concentrations for cellular effects can be established. This will be
important for future risk assessment.
Added value of
the cooperation: Both groups have been studying the genotoxicity of mycotoxins
in the past using partly complementary techniques. The group of J. Fink-Gremmels
has developed engineered cell lines in which the biotransformation-dependent
mutagenic response to OTA exposure could be demonstrated by means of a reporter
gene and subsequent sequence analysis. They also set up the Comet Assay for use
in primary cell culture systems. The group of G.Degen uses unscheduled
DNA-synthesis in primary cell cultures from human urothelial tissue and in
porcine urinary bladder epithelial cell cultures and studies cell-type specific
susceptibility to toxin induced oxygen radical formation and the expression of
cell specific defence mechanisms.
A4. Interactions of dietary iodine deficiency with
neonatal PCBs on thyroid function and brain development in rats
Winneke (Düsseldorf) / Kleinjans (Maastricht)
Severe iodine deficiency can result in miscarriage,
stillbirth, and congenital abnormalities. Iodine is required for the synthesis
of thyroid hormones. These hormones, in turn, are required for brain
development. Polychlorinated biphenyls (PCBs) are known to induce neurochemical
and behavioural disruptions during the early development of humans and
experimental animals. The hypothesis underlying the project predicts that
PCB-related cognitive impairment is brought about by PCB-induced hypothyroidism.
By combining an established iodine-deficiency model in rats with an established
developmental PCB-exposure model the hypothesis will be tested that the
combination of iodine deficiency with low-level PCB-exposure during early brain
development will produce overadditive interaction in terms of hypothyroid
effects and - consequently - impaired brain development.
Added value of the cooperation: The two laboratories contribute
complementary research interests and experience having as the common denominator
their longterm work on biological effects of polyhalogenated compounds. The
Division of Neurobehavioral Toxicology (Winneke) has a documented
expertise in neurobehavioral, neurophysiological and neuroendocrine
effects of PCBs, whereas the Department of Risk Analysis and Toxicology
(Kleinjans) contributes its expertise on thyroid dysfunction including thyroid
hormone measurement, measurement of PCB metabolites and PCB risk
assessment.
A5. Rapid non-genomic actions of testosterone:
Intracellular signalling mechanisms and isolation of the plasma membrane
receptor of testosterone
Wunderlich
(Düsseldorf) / Rietjens (Wageningen)
Steroid hormones, in particular testosterone and
testosterone derivatives, are widely used in animal production - legally in
U.S.A., illegally in Europe. Adverse effects for meat consumers are currently
considered negligible Also there is an enormous testosterone abuse by athletes
and bodybuilders. Testosterone acts through intracellular androgen receptors
(iAR) on gene expression of cells. Recent evidence, however, indicates that
testosterone can also signal through unconventional membrane testosterone
receptors (mTR) on the cell surface. The aim of this project is to isolate and
characterize such mTR. The project of the Dutch partner investigates the
interactive effects of testosterone and other anabolic agents through iAR at the
level of gene expression.
Added value of the
cooperation: The projects of both groups complement each other and have
synergizing effects in several different aspects. The Dutch group investigates
the interactive effects of testosterone and other anabolic agents on the level
of gene expression using DDRT-PCR and PCR-assisted subtractive hybridization.
Furthermore, they have developed a reporter gene assay allowing the
specific quantification of iAR-mediated effects. The mTR+-iAR--IC21 cells from
the German laboratory will be used to study the mTR-mediated effects of
real-life (veterinary) samples obtained by the Dutch group. At a later stage,
when we have cloned and characterized the mTR, the German student will
investigate the effect of mTR on testosterone effects mediated through iAR on
gene expression in the Dutch group.
B1. Pulmonary inflammation and systemic effects due to
ambient particulates
Borm
(Düsseldorf) / Bast (Maastricht)
Epidemiological studies have shown that exposure to ambient
air pollution, including (ultra)fine particulates is well known to increase
mortality and morbidity. Current hypotheses suggest that these particles induce
inflammatory responses, such as the influx of neutrophils (PMN) to the lung and
affect systemic mechanisms such as blood coagulation . It is the purpose of this
study to investigate the effect of instillation of ambient particles on (i) PMN
recruitment/adhesion and PMN induced toxicity in the rat lung, (ii) to evaluate
particle translocation, and (iii) the release of vasoactive mediators from the
lung. As a model the isolated perfused rat lung (constant flow) will be used,
perfused with suspensions of neutrophils (PMN) isolated from human blood. Effect
parameters are PMN adhesion and migration, lung and perfusate mediators of
inflammation and vasoaction (MPO, NO, ACE, histamine)and effects of perfusate on
isolated target tissues (heart, aorta). The model will use anti-oxidants
pre-treatment along with (ambient) particle instillation to
ameliorate inflammation and protective capacity of the lung. We hypothesize that
migration of inflammatory cells causes changes in lung permeability that allows
translocation of ultrafine particles, and that anti-oxidants can inhibit these
effects.
Exposure to ambient air pollution,
including (ultra)fine particulates, SO2 and NO2 increases mortality and
morbidity. One of the current hypotheses is that these factors induce
inflammatory responses, challenge anti-oxidant responses in the lung and affect
systemic mechanisms such as blood coagulation. It is the purpose of this study
to investigate the effect of anti-oxidant modulation in the lung on leukocyte
influx and leukocyte-induced toxicity after exposure to various ambient air
pollutants. As a model the isolated perfused rat lung will be used. Effect
parameters are vascular pressure, lung weight, leukocyte adhesion and migration,
anti-oxidant levels and oxidative DNA damage. The model will use Se-depletion,
vitamin E depletion and ambient particle instillation. We hypothesize that
anti-oxidant levels in the lung as modified by nutritional modification affect
the influx and migration of inflammatory cells, the subsequent damage and
release of vaso-active mediators.
Added value of the
cooperation: The two groups have collaborated for a large number of years and
contribute expertise from highly different laboratories. The IUF (Borm) is
a lab which has an accent towards molecular-biological and histopathological
techniques. The UM (Bast) is equipped to perform pharmacological experiments on
lung perfusate as well as to determine anti-oxidant status and chemical
degradation. In addition, the PhD will acquire knowledge and expertise in
complementary areas as Toxicology-Risk assessment (IUF) and pharmacology-dietary
modulation (UM).
B2. Role of dietary flavonoids in the adaptation of
antioxidant enzymes to prooxidants and proinflammatory mediators
Kahl (Düsseldorf) / Bast (Maastricht)
Flavonoids present in the diet are assumed to protect
consumer health by their antioxidative action because many degenerative diseases
have been linked to oxidative stress. Exogenous antioxidants may interfere with
the adaptive alterations of gene expression, e.g. the induction of antioxidant
enzymes, which occur in response to exposure to prooxidative and proinflammatory
conditions. In addition, exogenous antioxidants may possess prooxidative
properties themselves. It is the aim of the present project to examine whether
flavonoids encountered in the diet inhibit the induction of antioxidant enzymes
by prooxidants and proinflammatory cytokines and to elucidate the
structure-activity relationship involved. In addition, it will be attempted to
get insight into the signaling pathways leading to antioxidant enzyme induction
by prooxidants.
Added value of the cooperation: The
two collaborating laboratories are specialized in complementary fields.
While the laboratory of A. Bast in Maastricht has a broad background in
structure-activity studies of flavonoids and will supervise the choice of suited
flavonoids for the project and study their antioxidant/prooxidant balance, the
regulation of antioxidant enzymes is a main topic in the laboratory of R. Kahl
in Düsseldorf where molecular biological methods such as Northern blotting, EMSA
and transfection will be provided for the cell culture experiments.
B3. Cooperative interactions of antioxidant
micronutrients
Sies and Stahl
(Düsseldorf) / Bast (Maastricht)
Antioxidants interact synergistically and thus balanced
mixtures of dietary antioxidants may be superior to an increased consumption of
a single compound in disease prevention. In order to study cooperative
interactions and synergisms, unilamellar liposomes will be used to test
systematically combinations of antioxidants. The hydrophilic core space will be
loaded with hydrophilic antioxidants such as ascorbic acid; the surrounding
lipid bilayer can be loaded with hydrophobic compounds such a-tocopherol or carotenoids. The experiments
are designed to allow for the quantification of lipid peroxidation and
measurements of oxidative damage to proteins. Based on the results obtained with
the liposomal system appropriate antioxidant mixtures will be selected and
tested for antioxidant activity in cell culture. Additionally, ESR studies will
be performed to obtain information on the stability of radicals formed during
oxidation in order to get insight in mechanisms of antioxidant
interaction.
Added value of the cooperation: The
cooperating laboratories are both specialized in the field of antioxidant
research but their focus is on different classes of compounds and they apply
different techniques. Prof.Bast´s laboratory has a strong background regarding
structure-activity relationships of flavonoids and routinely uses ESR
spectroscopy to evaluate mechanisms of antioxidants action. Carotinoids and
tocopherols are a major research interest in the laboratory of Prof.Sies and
Dr.Stahl. Several models and cell culture systems are established to study
antioxidants biological effects and they are qualified in HPLC analyses. The
cooperation will provide additional scientific information and increase the
methodological knowledge of the PhD student.
B4. Immunomodulation and altered gene expression induced
by oral uptake of nickel (Ni) and zinc (Zn), respectively
Gleichmann (Düsseldorf) / van Loveren (Utrecht)
This project analyzes the beneficial dietary effects of
metal ions on two immunotoxicological mouse models established in Duesseldorf:
induction of allergic contact hypersensitivity (ACH) to Ni, and diabetes induced
with multiple low doses of streptozotocin (MLD-STZ). In both models, oral
administration of metal ions (Ni in the case of ACH, Zn in the case of
MLD-STZ-induced diabetes) prior to the disease-inducing treatment was shown to
be protective. Applying the DNA microarray technique to both disease
models will greatly expand the analytical scope for identification of the genes
and molecules, respectively, that are involved in the above-mentioned protective
effects of dietary Ni and Zn in that it allows to study a broad spectrum of
genes coding for different immunological as well as non-immunological
functions.
Added value of the cooperation: The two
coordinators, E. Gleichmann (MIU), and H. van Loveren (RIVM) know each
other for 15 years. They have cooperated in two EU projects on immunotoxicology.
The laboratories of E. Gleichmann and H. Gleichmann-Töpper have long-standing
expertise in models of allergic contact hypersensitivity and murine diabetes,
respectively, as well as in immunological techniques. The DNA microarray
technique to be used for screening gene expression at the mRNA level has been
established in the laboratory of H. van Loveren at RIVM. In addition, several
different types of array shall be used; these are currently being developed and
tested at RIVM.
B5. Purinergic receptors of human macrophages: Influence
of polychlorinated biphenyls and antioxidants on intracellular signal
transduction and redox systems
Wiegand and
Borm (Düsseldorf) / Bast (Maastricht)
While coplanar PCB are agonists of the aryl hydrocarbon (Ah)
receptor and are assumed to exert their actions on gene expression and cell
cycle via dioxin-like pathways the ortho-substituted non-planar PCB act via
non-dioxin-like effects which are poorly characterized. The hypothesis
underlying the present project suggests that these compounds interfere with
intracellular signal transduction. This increases in a concentration dependent
manner the purinergic receptor mediated cellular calcium levels and may thus
modulate apoptosis/growth regulation processes of the cell. It is the aim of the
project to a) more fully characterize the action of PCB on purinergic signal
transduction and b) to investigate whether antioxidants present in food can
interact with the PCB action. Synergistic or antagonistic actions on the
activation of purinergic receptors may influence proinflammatory responses and
growth regulation. This could be of great interest for preventive clinical
approaches.
Added value of the cooperation:
Purinergic signal transduction and its consequences can be studied in the two
cooperating laboratories by different methodological approaches. The group of
H.Wiegand is equipped to perform electrophysiological techniques and
microspectrofluorometric techniques whereas the group of A. Bast is
specialised on biochemical and pharmacological investigations including the
measurement of the redox status of cells and of second messenger concentrations
as well as the determination of cytokine and iNOS expression.
1. Introductory course in toxicology on CD-ROM, consisting of life recorded lectures in Real Audio and accompanying overhead sheets and slides in Powerpoint
A parallel course in basic toxicology is held in
each partner university during the first semester of the educational programme.
For this, a CD-ROM-based basic training course in toxicology has been developed
by the Dutch Postgraduate Education in Toxicology (PET). The course consists of
23 lectures ranging from toxicity mechanisms to organ-specific toxic effects,
roughly covering the topics from the handbook “Toxicology, principles and
applications” (eds.Niesink et al.). The students work on the study units
at their own PC. A helpdesk is available in case problems of technical or
educational nature should arise. Progress is verified in oral sessions with a
subgroup of the supervisor panel who are responsible for the study unit to be
discussed. Acquisition of the required knowledge will be tested by a written
examination at the end of the course.
2. Course modules
The major part of the educational programme consists of modular courses on central topics of toxicology with a duration of 1-3 weeks which is based on the Postgraduate Eduation Programme in Toxicology (PET) established in the Netherlands. Seven modules are part of of the common educational program of the Graduate College:
Laboratory courses of one week in laboratories at the home universities:
5. Common colloquia with Dutch PhD students on the
progress of students´ theses
to be held once
a year (2 days) in the presence of the supervisors. First colloquium:
10/02.
6. Common workshops in collaboration with EUROTOX
EUROTOX Training and Discussion sessions on specific topics
to be addressed by international experts (2 days). The workshops will be open
for scientists from outside the Graduate College and from other countries. First
EUROTOX workshop: "Diet and Cancer", 04/03.
7. Seminars to be held by visiting
scientists.