The Relative Semi-quantification of mRNA Expression as a Useful Toxicological Endpoint for the Identification of Embryotoxic/Teratogenic Substances

Toxicology in Vitro : an International Journal Published in Association with BIBRA
K BigotS Bremer

Abstract

Embryonic stem cells, which resemble the undifferentiated cells of the epiblast in a blastocyst, are able to differentiate into derivatives of the primary germ layers, including cardiomyocytes. The effects of embryotoxic/teratogenic compounds on the differentiation of cells was examined by semi-quantification of the mRNA expression using the RT-PCR protocol. Alpha and beta myosin heavy chain (alpha-MHC and beta-MHC, respectively) mRNA expression were chosen as tissue-specific markers, characteristic of early cardiac muscle development. Nine chemicals were investigated, chosen according to their in vivo embryotoxic/teratogenic potential in mice. The teratogens all-trans retinoic acid (RA), 5-fluorouracil (5-FU), hydroxyurea (HU), diphenylhydantoin (DPH) and caffeine (Caff) caused a significant reduction in MHC mRNA expression at a dose lower than that required for cytotoxicity. Saccharin (Sacc) had a similar effect, while penicillin G (PenG), isoniazid (Iso) and cytarabine (Ara-C) only showed an effect on MHC mRNA expression when the cells had a significant loss in viability. The inability to identify the strong teratogen Ara-C is related to the inappropriate target tissue.

References

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Citations

May 30, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·S BremerM Balls
Nov 8, 2001·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J RohwedelA M Wobus
Jul 2, 2011·Nature Protocols·Andrea E M Seiler, Horst Spielmann
Oct 12, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dorien A M van DartelAldert H Piersma
Oct 9, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Julieta M Panzica-KellyKaren A Augustine-Rauch
Jan 15, 2016·Chemical Research in Toxicology·Cindy X ZhangKaren Augustine-Rauch
Jan 6, 2016·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Karen Augustine-RauchJulieta M Panzica-Kelly
Sep 26, 2015·Toxicon : Official Journal of the International Society on Toxinology·Katherine J ReidFiona M Young
Aug 23, 2007·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Erica L LiebeltEdward J Stanek
Jun 12, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Esther de JongAldert H Piersma
Jun 26, 2010·Toxicology and Applied Pharmacology·Nicole I zur NiedenDerrick E Rancourt
Oct 11, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Annelieke K PetersJacques Van Gompel
Jul 3, 2008·Toxicological Sciences : an Official Journal of the Society of Toxicology·Annelieke K PetersPhilippe Vanparys

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