Learning Outcomes:

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

·         The importance of point mutations and chromosome changes in congenital and somatic disease

·         The male and female somatic and germ cell cycles

·         Stage sensitivity

·         Nuclear and mitochondrial organisation and changes

·         Potential targets for chemical interactions, such as the DNA, cell division cycle, spindle.

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

·         an understanding of the aetiology of cancer

·         an understanding of the processes involved in mutation, DNA repair and carcinogenesis

·         an understanding of the significance of non-genotoxic carcinogens versus genotoxic carcinogens

·         an understanding of the basis of carcinogenicity screening procedures and their limitations

·         a knowledge of the basic pathology of cancer and be able to relate this to the areas of concern within genetic toxicology

·         the ability to integrate knowledge of experimental mutagenesis, carcinogenesis, biochemistry and epidemiology into the process of risk assessment and extrapolate these findings to man.

·         Critical evaluation of the data and the ability to appraise the data in light o scientific reports.

Module content:

·         The basic structure of human genome, the karyotype, gene organisation, nuclear and mitochondrial organisation.

·         DNA structure, replication fidelity, base selection, enzymes and components of replication, mismatch repair correction of replication errors.

·         Cell cycles, mitosis and meiosis, male and female germ cell cycles. Targets for chemical interactions, cell division, spindle etc. What happens when the gene signals go wrong?

·         Types of gene mutations, base substitutions, insertions, deletions.

·         Micro/mini satellite changes. Their influence on human health.

·         Transposons and their significance, mechanisms of transposition.

·         Chromosome changes, types of rearrangements and modifications of the karyotype.

·         Gene mutation changes in human germ and somatic cells (including multifactorial disease), examples of gain and loss of function mutations

·         Imprinting discussion of the most relevant examples of diseases, nuclear and mitochondrial changes.

·         Chromosome changes, structural and numerical in human congenital disease, discussion of most relevant examples.

·         Genetic changes in human cancer, oncogene and tumour suppressor gene changes.

·         Chromosome structural and numerical changes in human cancers, e.g. such as translocation and aneuploidy in leukaemia’s.

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]

·         Alison, M. and Sarraf, C. (1997) Understanding Cancer

·         King, R. (1997) Cancer Biology

·         Ballantyne, B., Marrs, T. and Syversen, T. (2000) General and Applied Toxicology

·         Macdonald, F., Ford, C.H.J. & Casson, A.G. (2004) Molecular Biology of Cancer

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