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.
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.