The April 2018 Editor's Choice article is "Flow cytometric method for scoring rat liver micronuclei with simultaneous assessments of hepatocyte proliferation" by Svetlana L. Avlasevich, Sumee Khanal, Priyanka Singh, Dorothea K.Torous, Jeffrey C. Bemis, and Stephen D. Dertinger.
The incidence of micronuclei in hematopoietic cells (MN-RET) is one of the most widely used endpoints for evaluating chemical-induced in vivo genotoxicity. However, the collection of data from tissues capable of transforming chemicals into DNA-reactive intermediates was recommended recently in guidance documents developed by the International Conference on Harmonisation (ICH) Expert Working Group. Liver is considered as the most appropriate tissue because it is the main organ responsible for drug metabolism and usually contains the highest concentration of genotoxic intermediates relative to other tissues.
In their Editor’s Choice article, Avlasevich et al. reported an integrated method for determining cell proliferation and for detecting MN formation in rat hepatocytes (MNHEP). Using two different study designs (3-day and 14-day exposures), the authors found that two chemicals, diethylnitrosamine and quinoline, were negative in the MN-RET assay. Importantly, the same two chemicals induced dose-dependent increases in %MNHEP in rat liver, using either treatment schedule. Another important aspect of the work was that the %MNHEP values were comparable between flow cytometry-based and conventional microscopy-based MN assays, but the flow cytometry-based assay had a 100-fold greater data acquisition efficiency. This Editor’s Choice article, therefore, describes an important tool now available to researchers who wish to use automated MN scoring and cell proliferation determination in a tissue capable of metabolic activation, as part of a genotoxicity evaluation. Environ. Mol. Mutagen. 59:176-187, 2018. © 2018 Wiley Periodicals, Inc.