June’s Editor’s Choice article is "Image analysis of mechanistic protein biomarkers for the characterization of genotoxicants: Aneugens, clastogens, and reactive oxygen species inducers" (https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22374) by Sabrina Wilde, Nina Queisser, and Andreas Sutter.
Drugs or chemicals induce genotoxicity through a variety of mechanisms. The early detection of genetic damage and understanding the genotoxic mode of action provides a more in-depth safety assessment of drug candidates. Generally, clastogens induce DNA strand breaks, aneugens cause abnormalities in chromosome number, while reactive oxygen species (ROS) inducers cause DNA damage by producing excessive oxidative stress. Wilde et al. investigated whether post-translational modifications of proteins (PTMs) may be used as biomarkers to distinguish between different mechanisms of DNA damage.
In this proof-of-concept study, human lymphoblastoid cell line TK6 was exposed to fourteen reference genotoxic and nongenotoxic compounds in a 96-well plate format and the expression of PTM biomarkers were analyzed by immunofluorescence staining using an automated high content imaging technology. Increased expression of biomarkers 53BP1 (S1778) and FANCD2 (S1404) were shown to be an indicator of clastogen exposure; BubR1 (S670) and pH3 (S28) were induced by exposure to aneugens; the oxidative stress-associated protein Nrf2 (S40) was increased by ROS inducers; and acetylated p53 (K373) could be used for distinguishing between genotoxicants and nongenotoxicants. Thus, this Editor’s Choice article constitutes an important contribution to understanding the underlying mode-of-action of chemical-induced genotoxicity.