Learning Outcomes:

The aims of this module are that the students will be able to understand:

·         Principles of Phase 1 and Phase 2 metabolism.

·         Tissue specificity.

·         Relationships to activation of chemicals.

·         Activation preparation

·         Human variation.

·         Polymorphism/SNPs etc,

·         Individual genotyping and relationship to pharmaceutical development.

·         Engineered cell lines.

On the successful completion of the module the students should be able to assess study reports in the context of overall toxicological evaluation. They will:

·         understand the major pathways of xenobiotic metabolism in mammals

·         appreciate the significance of metabolism in genetic toxicology

·         appreciate the major species differences in metabolism and their significance for toxicity testing

·         understand the principles of toxicokinetics and be able to compare and contrast data sets.

·         be able to integrate knowledge of kinetics, dynamics and metabolism in the study of toxicity

Module content:

·         General principles covering the passage of xenobiotic chemicals through the mammalian body

·         Pharmacokinetics, pharmacodynamics and toxicokinetics.

·         Metabolism, principles of Phase I metabolism, oxidation, reduction, hydrolysis. Enzymes involved.
Examples of toxicology.

·         The Cytochrome P450s, history of identification and characterisation.

·         Basic biochemistry. Classification, cloning and sequencing.

·         Genetic factors, polymorphisms and SNP’s. Examples of variation. Environmental factors, enzyme induction, inhibition. Phase 1

·         Genetic factors, polymorphisms and SNP’s Examples of variation. Environmental factors, enzyme induction, inhibition. Phase 2

·         Experimental activation preparations for Phase ½ metabolism.

·         Influence of metabolism on effects of genotoxic exposure. Case studies

·         Genetic engineering of cell lines. Development and application.

·         Enzyme variation, genotyping, pharmaceutical development

·         Food industry. Overview and future development.

Pre-course Reading :

·         Friedberg E.C., Walker , G.C., Siede, W., et al (2006) DNA Repair and Mutagenesis, 2nd edn, pub: ASM Press (ISBN 1-55581-319-4) [core reading for all modules of the MTP]

·         Gibson, G. and Skett, P. (2001) Introduction to Drug Metabolism

·         Clark, B. and Smith, D., (2001) An Introduction to Pharmacokinetics

·         A number of relevant papers will be selected from the Mutation Research journal.