Pivotal role of micronucleus test in drug discovery

Book chapter, 2019

Early detection of adverse effects of novel compunds during drug discovery and development most probably reduce late stage failures, expenses and exertions for candidate drugs. Although the micronucleus (MN) test is one of the oldest techniques used in biochemical sciences for drug discovery. Flexibility of the technique for both in vitro and in vivo applications and practicability for large scale samples in short time make the MN test an inevitable tool for chemical trails. Drug studies require a formulation that provides the highest exposure to detect clastogenic and aneugenic activities and thus analysis makes it possible to get the necessary safety margin to support clinical trials. The MN test is one of the most important tools of the genotoxicity test battery in preclinical studies to identify negative effects of compounds that induce numerical and structural chromosome alterations in wide spectrum concentrations. The MN assay can be applied various cell types in different protocols. For instance; the most recommended protocols are bone the marrow micronucleus analysis and the in vivo mammalian erythrocyte precursor assay. Also, the rodent ovary cells validation test is a very powerful approach to analyse side effects of a compound. Beside cell types, detection systems can be constituted to obtain a high throughput screening such as integrating flow cytometry analysis into the MN inspections. Since a new compound is needed for such an assay, the MN test can assess abnormalities earlier in the drug discovery pipeline, making structure/genotoxicity connection a possible system for drug characterization.