Aneugen Molecular Mechanism Assay: Proof-of-Concept With 27 Reference Chemicals.

ABSTRACT: A tiered bioassay and data analysis scheme is described for elucidating the most common molecular targets responsible for chemical-induced in vitro aneugenicity: tubulin destabilization, tubulin stabilization, and inhibition of mitotic kinase(s). To evaluate this strategy, TK6 cells were first exposed to each of 27 presumed aneugens over a range of concentrations. After 4 and 24 h of treatment, γH2AX, p53, phospho-histone H3 (p-H3), and polyploidization biomarkers were evaluated using the MultiFlow DNA Damage Assay Kit. The assay identified 27 of 27 chemicals as genotoxic, with 25 exhibiting aneugenic signatures, 1 aneugenic and clastogenic, and 1 clastogenic. Subsequently, a newly described follow-up assay was employed to investigate the aneugenic agents' molecular targets. For these expe

SUBMITTER: Bernacki DT 

PROVIDER: S-EPMC6657583 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature