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
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.
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 damage induction, DNA repair mechanisms and DNA damage signaling pathways 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 in the context of risk assessment for mutagenicity and carcinogenicity.
Outcomes (competences, 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.
Dr. J. Boei, LUMC dept. Human Genetics, Leiden
Dr. F. de Gruijl, LUMC dept. Dermatology, Leiden
Dr. N. de Wind, LUMC dept. Human Genetics, Leiden
Dr. G. Hendriks, LUMC dept. Human Genetics, Leiden
Dr. J. Jansen, LUMC dept. Human Genetics, Leiden
Dr. M. Nivard, LUMC dept. Human Genetics, Leiden
Dr. E. Rorije, RIVM, Bilthoven
Dr. W. Schoonen
Dr. H. van Attikum, LUMC dept. Human Genetics, Leiden
Dr. J. van Benthem, RIVM, Bilthoven
Prof. Dr. H. van Steeg, LUMC dept. Human Genetics, Leiden and RIVM, Bilthoven
Dr. H. Vrieling, LUMC dept. Human Genetics, Leiden
There will be no examination. Participants will be required to actively take part in discussions following the lectures and during the practical work and will give a short presentation about the outcome of the Ames test.
Coordinator: Ms.dr. M.J.M. Nivard
Duration: 1 week
ECTS credits: 1.5
Number of participants: 12-16
Period: for exact dates, please consult the current programme schedule
Fee: see tuition fees (includes reduced fees for PhD students)
Location: Leiden University Medical Centre (LUMC), dept. Human Genetics, Leiden