title: Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro.
abstract: The inhibition of neural crest cell (NCC) migration has been considered as a possible pathogenic mechanism underlying chemical developmental toxicity. In this study, we examined the effects of 13 developmentally toxic chemicals on the migration of rat cephalic NCCs (cNCCs) by using a simple in vitro assay. cNCCs were cultured for 48 h as emigrants from rhombencephalic neural tubes explanted from rat embryos at day 10.5 of gestation. The chemicals were added to the culture medium at 24 h of culture. Migration of cNCCs was measured as the change in the radius (radius ratio) calculated from the circular spread of cNCCs between 24 and 48 h of culture. Of the chemicals examined, 13-cis-retinoic acid, ethanol, ibuprofen, lead acetate, salicylic acid, and selenate inhibited the migration of cNCCs at their embryotoxic concentrations; no effects were observed for acetaminophen, caffeine, indium, phenytoin, selenite, tributyltin, and valproic acid. In a cNCC proliferation assay, ethanol, ibuprofen, salicylic acid, selenate, and tributyltin inhibited cell proliferation, suggesting the contribution of the reduced cell number to the inhibited migration of cNCCs. It was determined that several developmentally toxic chemicals inhibited the migration of cNCCs, the effects of which were manifested as various craniofacial abnormalities.
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Makoto
authors.identifier: http://orcid.org/0000-0002-2903-5114
authors.initials: M
authors.lastname: Usami
authors.affiliation: School of Pharmaceutical Sciences, Toho University, Chiba, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Mitsunaga
authors.affiliation: Division of Medical Devices, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Mina
authors.initials: M
authors.lastname: Takamatu
authors.affiliation: School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Shugo
authors.initials: S
authors.lastname: Kazama
authors.affiliation: Division of Pharmacology, National Institute of Health Sciences, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Irie
authors.affiliation: United Graduate School of Agricultural Science, Gifu University, Gifu, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Doi
authors.affiliation: School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D009432:Neural Crest / Q000166:cytology* / Q000187:drug effects*; D051381:Rats
chemical_list: D009153:Mutagens
keywords: developmental toxicity; embryo; migration assay; neural crest cell; rat