Micheline
Kirsch-Volders
Position: Professor
Prof. Volders has 30 years of research and 15 years of
management experience in the study of in vitro and in
vivo genotoxic effects of chemicals: about 180 papers were
published on these subjects.
She has contributed to many European research programmes: EEC
BIOMED (solid tumour cytogenetics), EEC-STEP (biomonitoring,
aneuploidy), EU-Environment (aneuploidy) and EU-Nuclear fission
in collaboration with research laboratories throughout Europe
including UK, Germany, the Netherlands, Denmark, Sweden, Finland,
Italy and Greece.
She also coordinated a COPERNICUS project on neurotoxicity with
partners from Poland and Hungary and a EU-Environmental project on
in vivo induction of micronuclei in the gut.
Within EU-FP5, she was involved in 3 programmes: PEPFAC
(QLK4-CT-2000-00058), CancerRiskBiomarkers (QLT4-CT-2000-00628
and QLK4-CT-2002-02831) and CHILDRENGENONETWORK
(QLK4-CT-2002-02198).
At the present time within FP6, the laboratory is also a member of
the ECNIS Network of Excellence.
Prof. Kirsch-Volders is president of the European Environmental
Mutagen Society (EEMS).
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Ilse
Decordier
Position: Post doc
During
her PhD (defended in March 2006) she focused on the
relation between ploidy control and apoptosis in human cells after
in vitro exposure to
microtubule inhibitors.
Currently
she is working as a postdoctoral fellow within an EU-project on
Newborns and Genotoxic exposure risks (NewGeneris).
Within this framework, she is involved in a workpackage studying
biomarkers of carcinogenic
risk
and phenotypic effects. She is coordinating the interlaboratory
sampling and analysis
of maternal and umbilical cord blood lymphocytes for micronuclei
and markers of apoptosis/necrosis and in vitro proliferation
rates.
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Laetitia Gonzalez
Position: PhD student
Physico-chemical determinants of toxicity : a rational
approach towards safer nanostructured materials
Nanomaterials are engineered structures
with dimensions of 100 nm or less, which achieve unique
mechanical, optical, electrical and magnetic properties. Although
these materials are already widely used in different applications,
ranging from cosmetics and tires to medical applications, concerns
about their effects on human health, in occupational settings and
possibly for the consumer and the general population at large, are
raised. A number of research reports have pointed towards their
harmful effects on different target organs, which include the
respiratory tract, the brain, the cardio-vascular system, the skin
and the liver. Understanding how nanomaterials exert toxic effects
and identifying physico-chemical determinants of nanomaterials
toxicity are the main issues that will be investigated in
collaboration with three other research groups (UCL-TOXI,
KULeuven-LUNG and KULeuven-COK).
A single model material, i.e. silicon-based
nanoparticles (SNP), will be used to assess genotoxicity and
apoptosis in epithelial, endothelial and mesothelial cells by a
reverse combinatorial approach. These in vitro data together with
the in vitro data from the other research groups, concerning the
production of inflammatory mediators by macrophages and platelet
aggregation and coagulation, will be used to develop a paradigm
for SNP toxicity that will be critically tested in vivo in two
species (rat and mouse) with contrasting sensitivity.
Additionally, the cellular and molecular mechanisms underlying the
response to SNP toxicity will be investigated, focusing on
interactions with the cytoskeletal proteins, induction of
aneuploidy, effects on the DNA repair capacity and on cellular
trafficking.
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Noömi Lombaert
Position: PhD student
Molecular
and genetic research for the mechanisms leading to toxicity and
apoptosis induced by cobalt-containing dust
Occupational exposure to cobalt-containing dust has been
associated with pulmonary toxicity including asmathic reactions,
fibrosing alveolitis (hard metal disease) and lung cancer. The
mechanisms for lung fibrosis versus cancer induction by hard metal
(WC-Co) are not yet clearly understood. While the asthmatic
responses are caused by cobalt species, the development of cancer
and fibrosing alveolitis is mainly ascribed to the simultaneous
exposure to cobalt and tungsten carbide particles. In vitro in
human PBMC and in vivo in rat pneumocytes, it has been shown that
WC-Co is inducing genotoxicity and apoptosis.
To define the underlying molecular mechanisms of hard metal
exposure in peripheral blood mononucleated cells (reporter cells
for biomonitoring), primary monocytes and alveolar epithelial
cells A549 (target cells for cancer inducing effects on the lung)
high-throughput transcriptional analysis tools -such as microarray
and RT-qPCR- are applied. As such, the global modulated gene
expression levels can be analyzed, and the involvement of new
genes can be evaluated. A better knowledge of the different
signalization pathways would give a better understanding about the
modulating effects of apoptosis on the induction of fibrosis and
lung cancer
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Raluca Mateuca
Position: PhD student
Genetic
polymorphisms and frequency of genotoxicity biomarkers in
occupationally exposed people
Inter-individual variability in
human responses to mutagens/carcinogens has been the subject of
much research lately. It
is well known that humans differ in their susceptibility to
cancer. This may be due to a number of factors, including health,
nutritional status, gender and genetic background. Inherited (or
aquired) genetic polymorphisms in genes responsible for the
metabolic activation and detoxification of mutagens/carcinogens,
for the fidelity of DNA replication (mismatch repair), DNA repair
and/or chromosome segregation have the potential to influence the
amount of individual DNA damage and the cancer risk. Therefore,
the identification of higher risk individuals caring genetic
polymorphisms responsible for increased activation, and reduced
detoxification/repair of mutagen/carcinogen-induced DNA damage has
substantial preventive implications as these individuals could be
targeted for primary cancer prevention.
To evaluate the influence of
genetic polymorphisms on the baseline or induced frequency of
genotoxicity biomarkers [chromosomal aberrations (CAs),
micronuclei (MN), sister chromatid exchanges (SCE), high frequency
cells (HFC), Comet tail (TD)] in human lymphocytes, several
occupational exposure studies have been performed (e.g.,
cobalt-containing dust, ionizing radiation, styrene, arsenic
compounds, mustard gas). For each study, the influence of genetic
polymorphisms on the levels of genotoxicity biomarkers was modeled
by means of regression analysis (e.g., multivariate, Poisson) and
adjusted for age, gender, smoking/nutrition status, and
occupational exposure. The effect of genetic variation on the
levels of genotoxicity biomarkers will be further evaluated by
pooling together the individual occupational exposure datasets.
This approach has the advantage of increasing the statistical
power and resolving discrepancies among individual studies.
Assessment of the possible modifying effect of genetic
polymorphisms on the levels of genotoxicity biomarkers, could
provide a valuable tool for policy makers and regulatory bodies in
assessing the various factors contributing to individual DNA
damage and cancer risk.
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Gina Plas
Position: Lab Technician
Lab management and technical support.
Techniques: Cell culturing, PCR genotyping,
micronucleus test (manual+automized scoring), sister chromatid
exchanges test, chromosomal aberration test, ...
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Sam Roesems
Position: Lab Technicien
Lab management and technical support.
Techniques: Cell culturing, micronucleus test
(manual+automized scoring), sister chromatid exchanges
test, ...
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Veerle
Amerijck
Position: Master level student
Susceptibility
of premature born babies to oxidative damage
The aim
of this project is to investigate the susceptibility of preterm
neonates for oxidative damage, including the comparison with their
mother. Our hypothesis is that the enzymatic protection (including DNA repair)
occurs less efficient in preterm neonates as compared to term
infants. Moreover other antioxidant systems, such as vitamin C
and/or E, could be present in preterm babies.
Blood
samples will be collected at the
St-Pierre
University
Hospital
in
Brussels
. PBMC from the umbilical cord of the neonates and PBMC from
venous blood of the mothers will be exposed in
vitro to hydrogen peroxide (H2O2), a
compound that is used as a model mutagen for oxidative stress and
damage. The in vitro
genetic susceptibility for H2O2 of the
mother-premature daughter pairs will be compared taking into
account genotypes for relevant DNA repair (hOGG1,
XRCC1, XRCC3, XPD) and folate metabolism (MTHFR)
polymorphisms. After in
vitro challenge with H2O2 the repair
capacity will be assessed by the Comet assay and chromosome/genome
mutations by the cytokinesis-block MN assay.
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Annelies Breynaert
Position: Master level student
Age dependent interactions between genotoxic
and immunotoxic effects
The aim of my project is to investigate the
interactions between age and genotoxic and immunotoxic effects.
The working hypothesis is based on a study of the dual function of
the GSTT1 gen in colon cancer. In
“younger” patients detoxification of the carcinogen and
darmkanker. In ‘jongere’ patiënten treedt detoxificatie van
het carcinogeen op en modulatie modulation to an inflammatory
respons is observed. In “older”
patients the immune reaction decreases with ages leading to a
higher accumulation of mutations and thus a reduction of the
surviving chances. Our question is: for an unchanged genotype,
does the phenotype for detoxification (GSTs) and the immune
response change with age?
Therefore blood of newborn daughters, their
mothers of 25 years and women of 50 to 60 years old will be
exposed in vitro to the
mutagen BPDE
(Benzo(a)pyrene–trans-7,8-dihydrodiol-9,10-epoxide). After
in vitro challenge with
this compound the immune response will be analysed taking into
account genotypes for relevant detoxification (GSTs) and immune
response and detoxification polymorphisms. These genotypes will be
compared with the phenotype for immune response and
detoxification, by measuring the enzyme activity.
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Kim Vande Loock
Position: Master Level student
Differential sensitivity of newborn daughters
exposed to polycyclic aromatic hydrocarbons
Recent research showed increased susceptibility of newborns
for certain pollutants like polycyclic aromatic hydrocarbons
(PAHs). One of the most studied PAHs is benzo(a)pyrene (B(a)P).
B(a)P can be converted by enzymes to a reactive metabolite (BPDE)
which can cause DNA damage by forming adducts. The purpose of this
project is to check the capacity of newborn daughters to repair
the in vitro DNA damage induced by BPDE. Moreover we want to know
if the repair capacity of BPDE induced DNA damage is comparable
between newborn daughters and their mothers.
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