Combination of multiple neural crest migration assays to identify environmental toxicants from a proof-of-concept chemical library.

Combination of multiple neural crest migration assays to identify environmental toxicants from a proof-of-concept chemical library. Arch Toxicol. 2017 May 05;: Authors: Nyffeler J, Dolde X, Krebs A, Pinto-Gil K, Pastor M, Behl M, Waldmann T, Leist M Abstract 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. So...
Source: Archives of Toxicology - Category: Toxicology Authors: Tags: Arch Toxicol Source Type: research