The importance of developing in vitro tests for embryotoxicity is discussed, and ECVAM's work with its collaborators is summarised. Studies are in progress to find new endpoints for use in the scientifically validated embryonic stem (ES) cell test, so that the potential for chemical effects on endodermal, mesodermal and/or ectodermal differentiation can be identified. This involves, inter alia, the use of genetically modified ES cells.
SpielmannH., PohlI., DoeringB., LiebschM., & MoldenhauerF. (1997). The embryonic stem cell test, an in vitro embryotoxicity test using two permanent mouse cell lines: 3T3 fibroblasts and embryonic stem cells. In Vitro Toxicology10, 119–127.
2.
GenschowE., SpielmannH., ScholzG., SeilerA., BrownN., PiersmaA., BradyM., ClemannN., HuuskonnenH., PaillardF., BremerS., & BeckerK. (2002). The ECVAM international validation study on in vitro embryotoxicity tests: results of the definitive phase and evaluation of prediction models. ATLA30, 151–176.
3.
WilsonJ.G.Current status of teratology: general principles and mechanisms derived from animal studies. In Handbook of Teratology: General Principles and Etiology. Vol. 1 (ed. WilsonJ.G., & FraserF.C.) pp. 47–74. New York, NY, USA: Plenum Press.
4.
BremerS., PellizzerC., CoeckeS., PaparellaM., & CatalaniP. (2002). Detection of the embryotoxic potential of cyclophosphamide by using a combined system of metabolic competent cells and embryonic stem cells. ATLA30, 77–85.
5.
BremerS., & BigotK. (1997). Comparison of three different toxicological endpoints in the establishment of an in vitro embryotoxicity screening system based on embryonic stem cells. European Journal of Cell Biology74, 26.
6.
BigotK., De LangeJ., ArcherG., ClothierR., & BremerS. (1999). The relative semi-quantification of mRNA expression as a useful toxicological endpoint for the identification of embryotoxic/terato-genic substances. Toxicology in Vitro13, 619–623.
7.
KolossovE., FleischmannB.K., LiuQ., BlochW., Viatchenko-KarpinskiS., ManzkeO., JiG.J., BohlenH., AddicksK., & HeschelerJ. (1998). Functional characteristics of ES cell-derived cardiac precursor cells identified by tissue specific expression of the green fluorescent protein. Journal of Cell Biology14, 2045–2056.
8.
FleischmannM., BlochW., KolossovE., AndressenC., MuellerM., BremG., HeschelerJ., AddicksK., & FleischmannB.K. (1998). Cardiac specific expression of the green fluorescent protein during early murine embryonic develoment. FEBS Letters440, 370–376.
9.
BremerS., WorthA., PaparellaM., BigotK., KolossovE., FleischmannB., HeschelerJ., & BallsM. (2001). Establishment of an in vitro reporter gene assay for developmental cardiac toxicity. Toxicology in Vitro15, 215–223.
10.
PaparellaM., KolossovE., FleischmannB., HeschelerJ., BallsM., & BremerS. (2002). The use of quantitative image analysis in the assessment of in vitro embryotoxicity endpoints based on a novel embryonic stem cell clone with endoderm-related GFP expression. Toxicology in Vitro16, 589–597.
11.
ArmstrongL., LakoM., LincolnJ., CairnsP.M., & HoleN. (2000). mTert expression correlates with telomerase activity during the differentiation of murine embryonic stem cells. Mechanisms of Development97, 109–116.
