Aim of the course
This module is focussed on understanding mechanisms of toxicity at the molecular level.
Content of the course
In a number of lectures and case-studies, molecular mechanisms underlying (organ-selective) toxicity and carcinogenicity will be discussed. Special emphasis will be on the role of drug metabolism and bio(in)activation in toxicology. Topics include: multiplicity and properties of drug-metabolising enzymes (cytochrome P450, glutathione S-transferases and others); experimental approaches to characterize enzymes involved in drug metabolism; clinical and toxicological consequences of genetic polymorphisms of drug metabolising enzymes; chemical and biological properties of reactive intermediates responsible for toxicity; mechanisms underlying idiosyncratic drug reactions; novel computational approaches to predict drug metabolism and toxicity; and, mechanisms determining organ-selective toxicity. Participants should have a sound knowledge of basic organic chemistry to be able to fully profit from this course.
Outcomes (competences, skills)
• Knowledge on multiplicity and properties of biotransformation enzymes, and their role in bioactivation and bio-inactivation of drugs and other chemicals;
• Knowledge on the experimental approaches used to identify individual biotransformation enzymes involved in bioactivation and inactivation reactions;
• Knowledge on the experimental approaches to identify and quantify metabolites, reactive intermediates and adducts to cellular target molecules;
• Knowledge of the risk factors, which might determine inter-individual susceptibility to drugs and other chemicals, including genetic polymorphisms, drug-drug interactions (inhibition, induction), environmental factors.
At the end of the week (Friday afternoon), the participants will give an oral presentation on the theoretical assignments, which will subsequently be discussed.
Coordinator(s): Dr. J.N.M. Commandeur
Duration: 1 week
ECTS credits: 1.5
Number of participants: 20-30
Period: for exact dates, please consult the current programme schedule
Fee: see tuition fees (includes reduced fees for PhD students)
Location: LACDR, Dept. Molecular Toxicology, Pharmacochemistry, Vrije Universiteit, Amsterdam