Improved In Vitro Genotoxicity Testing to Reduce Animal Testing
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In conjunction with the University of Manchester, Gentronix has been granted a research award of £133,024 by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs).
One of nine awards made by NC3Rs in 2006, the funding will be used to develop a novel genotoxicity assay in a human liver cell line, designed to reduce the use of live animals in drug development.
Safety testing of new pharmaceuticals includes screening for the potential to cause cancer. The existing mammalian cell in vitro tests are highly sensitive so most carcinogens are identified, but many safe compounds are also falsely identified as potential carcinogens.
Because this can lead to needless loss of useful new drugs, live animal tests are still conducted when there is only one in vitro positive result. By using a new high specificity human cell-based genotoxicity test, the aim will be to reduce the number of compounds tested on animals.
Preliminary validation studies with a new human cell genotoxicity test have demonstrated an ability to detect all direct acting mechanistic classes of genotoxic chemicals, as well as aneugens and compounds disrupting DNA replication and repair.
Results recently reported by Gentronix and GSK in Mutation Research show the new assay to have sensitivity comparable to that of existing mammalian in vitro genotoxic assays, but uniquely combined with very high levels of specificity.
However, some compounds (promutagens) are only carcinogenic after passing through the liver, and regulations require a separate test to be performed using liver tissue extracts.
The NC3Rs research award will enable the development of the new test in a liver cell line to give a better early indication of genotoxicity while reducing animal testing. These results will be compared with those of the existing tests using liver extracts.
As well as providing a valuable new tool to confirm positive data from existing tests, the new high specificity human cell-based genotoxicity test aims to reduce the number of compounds going on to animal testing.
The use of this new test will not only reduce the number of animals used in genotoxicity testing but also reduce the considerable costs of conducting animal tests.
