An increased frequency of micronucleated cells is a biomarker of genotoxic effects that can reflect exposure to agents with clastogenic (chromosome breaking; DNA as target) or aneugenic (aneuploidogenic; effect on chromosome number; mostly non-DNA target) modes of action [ 43].
Such targeted or non-targeted modes of action are analogous to those of histone acetylases and other chromatin-modifying activities that are involved in transcriptional regulatory mechanisms (Struhl, 1998).
Various experimental studies suggest a multi-target mode of action for Padma 28 and Padma Circosan, which, except the omission of one ingredient (Aconiti tuber), is identical to Padma 28.
Importantly, there was correlation between pharmacokinetics analysis of compound exposure and pharmacodynamics analysis based on anti-IgD-induced CD69 expression on B cells (B220+), indicating on-target mode of action.
If this hypothesis is correct, it should be possible to use information derived from the drug development process, such as molecular target, mode of action, effective dose and physicochemical properties, together with genomic and physiological knowledge of the non-target organism, to predict the likelihood of an effect occurring, assuming relevant exposure.
As such, one could also hypothesize that the activities (the relative abundance and interactions) of these signature genes could be part of drug targets, or mode-of-action (MoA), as these genes can be used to explain tumor types and differences in chemotherapeutic response of patients.
Data obtained from either in vitro cell-based or in vivo systems-based DNT alternatives may provide insights into relevant cellular, molecular, and regional targets, informing mode-of-action hypotheses and identifying potentially vulnerable developmental stages, thereby refining and reducing mammalian in vivo testing.
In view of the worldwide rise and spread of antibiotic resistance, the identification of novel targets and modes of action of antibacterial compounds is a vital objective (Levy & Marshall, 2004; Wright, 2007).
Thus, in EDA, bioassays are considered as tools to sensitively detect chemicals with similar biological targets or modes of action.
Understanding their biological targets and modes of action will be essential to design improved second-generation compounds.
