Public Funding for Gentronix Limited

Continued innovation by the diverse chemical sectors is expected to provide new, better, and more effective medicines, herbicides, pesticides and consumer products. The public expects these to be safe as well as effective. Cancer risk is perhaps the most concerning. The most potent carcinogens are mutagens: compounds that alter the DNA sequences in our cells. Tests that identify mutagens using bacteria or human/animal cells grown in laboratories have been in use since the 1970s, and they have been effective in ensuring chemical safety. However, these tests often produce positive results for non-mutagens - 'false positive'. This mean that many potentially useful or even life-saving chemicals will have been lost due to misplaced safety concerns. To identify false positives, the number of animals used before exposing humans, is increased - often finding that the compounds are indeed carcinogens. The obvious solution is the development of more accurate cell-based tests, which will reduce this use of animals and bring more useful and safe products for people to use: and that is the ambition of this project.

The human genome is complex and well protected by an array of systems that sense damage, and initiate repair. When damage is overwhelming, cells are usually forced into suicide to minimise the generation of viable mutant cells that might develop into tumours. Direct DNA damage is not the only threat to the genome. Tissues such as liver, kidney, muscle etc are different because they express different subsets of genes from the same human genome. Active genes are more loosely packaged than inactive genes; inactive genes are more likely to have modified DNA bases compared to active genes. This regulation, above the DNA sequence, defines the science of epigenetics. The distinctive and lifethreatening cells found in tumours also have distintive epigenetic signatures, and in this project it is aimed to determine whether it is possible to detect epicarcinogens in a simple lab test that can detect changes in these signatures of gene expression.