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Fig. 3 | Genes and Environment

Fig. 3

From: Advantages of evaluating γH2AX induction in non-clinical drug development

Fig. 3

In this case from the late screening stage, 6 pharmacologically promising compounds, from which the final candidate for GLP studies was to be selected, all showed positive in the MNT in vitro screening in TK6 cells, which meant that a critical decision-making point was whether the compounds were aneugenic or clastogenic. The conventional strategy would use an in vitro FISH analysis with centromeric DNA probes as the next step, but because the FISH assay is laborious and time-consuming, practically speaking only one or two compounds would be investigated. Therefore, development would have to continue without investigating the risk of clastogenicity in all of the compounds. On the other hand, the advanced strategy includes measuring γH2AX induction in TK6 cells by FCM. As a result, all the 6 compounds were found to be aneugens prior to conducting FISH analysis; therefore, the γH2AX assay could effectively reduce the risk that the compounds would be revealed to be clastogens in the later FISH analysis

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