Effects of 13 developmentally toxic chemicals on the migration of rat cephalic neural crest cells in vitro

  • Makoto Usami
    Division of Pharmacology National Institute of Health Sciences Tokyo Japan
  • Katsuyoshi Mitsunaga
    School of Pharmaceutical Sciences Toho University Chiba Japan
  • Atsuko Miyajima
    Division of Medical Devices National Institute of Health Sciences Tokyo Japan
  • Mina Takamatu
    School of Veterinary Medicine Azabu University Kanagawa Japan
  • Shugo Kazama
    School of Veterinary Medicine Azabu University Kanagawa Japan
  • Tomohiko Irie
    Division of Pharmacology National Institute of Health Sciences Tokyo Japan
  • Osamu Doi
    United Graduate School of Agricultural Science Gifu University Gifu Japan
  • Tatsuya Takizawa
    School of Veterinary Medicine Azabu University Kanagawa Japan

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Abstract

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.

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