Timothy Gant – MRC Toxicology Unit , Leicester University
Skin cancers are very common in humans – with around one million cases/year in the US – and their development can be affected by stimulators of growth such as certain chemicals. Although initiation is clearly extremely important, clonal expansion (promotion) and irreversible mutations (progression) ultimately determine the outcome of carcinomas. Tumour development is characterised by changes in the expression of many genes. Identifying these changes would improve understanding of the critical steps in the pathway. The researchers have access to new technology allowing fragments of thousands of genes to be put on glass slides and compared with the amounts of messages for these genes in tissue samples. They aim to explore the complex patterns of gene expression during promotion phases in mouse models of skin cancer. The project will include an evaluation of the effect of the dioxin 2,3,7,8-TCDD, on cancer development in mice. Similar studies will be carried out on human skin cells in vitro, and gene expression profiles will be analysed to see if they are similar to those seen in the early stages of tumour development. This will be helpful in establishing more refined estimates in risk evaluation of dermal-active chemicals in humans.
K Ridd, S-D Zhang, RD Edwards, R Davies, P Greaves, A Wolfreys, AG Smith, TW Gant, Association of gene expression with sequential proliferation, differentiation and tumour formation in murine skin, Carcinogenesis 2006, 27, 1556-1566.
K Ridd, S Dhir, AG Smith, TW Gant, Defective TPA signalling compromises HaCat cells as an in vitro keratinocyte carginogenesis model, Environmental Health Perspectives, submitted.