Course: Mutagenesis and Carcinogenesis
In this module, we will
focus on i) the different types of damage that can be formed in the DNA of our
cells either spontaneously or because of exposure to DNA damaging agents in the
environment, ii) the cellular defense mechanisms that preserve genetic
integrity and iii) the biological consequences of non-repaired DNA damage in
particular the induction of mutations in relation to the development of cancer
Content of the course
Preservation of genetic information
(DNA) is of prime importance to all living systems. The integrity of the genome
is continuously threatened by endogenous metabolic processes and by exogenous
agents of a chemical and physical nature that induce damage to the DNA.
Moreover, the induction of genetic alterations by DNA damage is the major
initiating and driving step in the process of carcinogenesis. To withstand the
harmful effects of DNA damage and to maintain genome integrity, cells are
equipped with an intricate network of DNA damage response pathways.
Lectures
will deal with the basic principles of several cell biological aspects such as
metabolic activation/deactivation of chemicals, DNA repair mechanisms and cell
cycle processes as well as the rationale and execution of short-term tests for
genotoxicity. The purpose of the practicals and workgroups is to familiarize
participants with short-term tests (STT) for genotoxicity and with molecular
techniques employed to analyze chemically-induced alterations in DNA.
Aim of the course
The
aim of the course is to familiarize participants with the mechanisms by which
DNA damage causes genetic alterations and cancer and the cellular processes
which protect human beings from the deleterious effects of DNA damaging agents.
Module
outcomes (competence, skills)
- The participant understands the mechanisms by
which different types of DNA damage may threaten the viability and/or genetic
integrity of cells.
- The participant knows the potency of short
term test in evaluation studies on mutagenicity and carcinogenicity.
- The participant understands the difference
between DNA damage and DNA mutation and the differential impact of hereditary
versus somatic mutations for enhancing cancer risk.
- The participant can deduce and explain the
consequences of defects in various cellular processes that aim to protect the
individual against cancer.
Examination
There
will be no examination. Participants will be required to actively take part in
discussions following the lectures and during the practical work.
Lecturers:
Dr. F. Darroudi: LUMC dep. of Toxicogenetics,
Dr.
B. Godthelp: LUMC dep. of Toxicogenetics,
Dr. J. Jansen: LUMC dep. of Toxicogenetics, Leiden
Dr.
A.G. Jochemsen: LUMC dep. of Molecular and Cellular Biology,
Dr.
M. Nivard: LUMC dep. of Toxicogenetics,
Dr.
A. Pastink: LUMC dep. of Toxicogenetics,
Dr.
J. van Benthem: RIVM, Bilthoven
Prof. Dr. H. van Steeg:
LUMC dep. of Toxicogenetics, Leiden
Dr. H. Vrieling: LUMC dep. of Toxicogenetics, Leiden
Dr. N. de Wind: LUMC dep. of Toxicogenetics, Leiden
Duration: 1 week
ECTS credits: 1.5
Period: 01/03
- 05/03, 2010
Fee: € 1,000.- (PhD students may
apply for the reduced rate of € 250.-)
Location:
Dept.
of Toxicogenetics
Einthovenweg
20
Building
2
2333 ZC Leiden, The Netherlands