Announcing the next ASCCT webinar
Combination of multiple neural crest migration assays to identify environmental
toxicants from a proof‑of‑concept chemical library
Thursday June 8, 2017
11:00 AM EDT
Registration is free but required. Register here:
Presenter: Johanna Nyffeler, In Vitro Toxicology and Biomedicine, University of
Many in vitro tests have been developed to screen for potential neurotoxicity.
However, only few cell function-based tests have been used for comparative
screening, and thus experience is scarce on how to confirm and evaluate
screening hits. We addressed these questions for the neural crest cell
migration test (cMINC). After an initial screen, a hit follow-up strategy was
devised. A library of 75 compounds plus internal controls (NTP80-list),
assembled by the National Toxicology Program of the USA (NTP) was used. It
contained some known classes of (developmental) neurotoxic compounds. The
primary screen yielded 23 confirmed hits, which comprised ten flame retardants,
seven pesticides and six drug-like compounds. Comparison of
concentration–response curves for migration and viability showed that all hits
were specific. The extent to which migration was inhibited was 25–90%, and two
organochlorine pesticides (DDT, heptachlor) were most efficient. In the second
part of this study, (1) the cMINC assay was repeated under conditions that
prevent proliferation; (2) a transwell migration assay was used as a different
type of migration assay; (3) cells were traced to assess cell speed. Some
toxicants had largely varying effects between assays, but each hit was
confirmed in at least one additional test. This comparative study allows an
estimate on how confidently the primary hits from a cell function-based screen
can be considered as toxicants disturbing a key neurodevelopmental process.
Testing of the NTP80-list in more assays will be highly interesting to assemble
a test battery and to build prediction models for developmental toxicity.
After registering, you will receive a confirmation email containing information
about joining the webinar.