Learning Outcomes:

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

·         Interaction of chemicals and radiations with genetic material

·         Exogenous and endogenous activities

·         Methods for detection of lesions

·         DNA repair activity, methods for the detection of activity

·         Structure/activity relationships

·         Conversion of a DNA lesion into gene and chromosome changes

·         Detection methods such as SSCP RSM FISH, CGH. Shuttle vectors

·         Mutation databases, mutation types and spectra

·         Relationships with cancer databases

·         Gene expression models

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

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

·         An understanding of the basis of mutagenicity screening procedures and their limitations

·         Extrapolation of experimental data to man.

·         The ability to integrate knowledge of mutagenesis, into the process of risk assessment

·         Critical Evaluation of the data.

Module content:

·         DNA modifications by ionising and non-ionising radiations

·         Chemically induced lesions, small adducts as illustrated by the alkylating agents.

·         Endogenous lesions, e.g. oxidative damage, the spontaneous lesion background.

·         Bulky adducts, e.g. polycyclic aromatic hydrocarbons such as benzo(a)pyrene, aflatoxins, synthetic molecules.

·         DNA reactive anti-cancer drugs, e.g. cis-platin, tamoxifen, non-DNA reactive anti-cancer drugs, e.g vinca alkaloids, taxol.

·         Lesion and adduct detection methods, 32P postlabelling, comet assay, immunological methods radiolabelled compounds, mass spectrometry.

·         Replication fidelity, mismatch repair, sensitivity to colorectal cancer. Base excision repair.

·         Nucleotide excision repair, post-replication and double strand break repair

·         Repair defective mutations. Human repair syndromes and their implications.

·         Detection methods for gene and chromosome changes such as SSCP, RSM, FISH, CGH.

·         The conversion of DNA lesions into gene and chromosome changes.

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]

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